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ABSTRACT TOPIC
DISEASE ORIENTED
HEMATOPOIETIC STEM CELL TRANSPLANTATION
ABSTRACT NO.: Q-195
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Functional activity of platelets and spatial thrombin generation after platelet concentrate transfusion in children after hematopoietic stem cell transplantation
E. Koltsova, A. Balandina, I. Demina, S. Radygina, F. Ataullakhanov, D. Balashov, M. Panteleev
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: platelet transfusion, hematopoietic stem cell transplantation, haemostasis, thrombin
Introduction. Allogenic platelet transfusions are important in clinical practice as an efficient treatment of persistent thrombocytopenia, which is a common complication after hematopoietic stem cell transplantation (HSCT).
Aim. The aims of this study are to investigate effects of platelet transfusion on platelet functions, spatial clot growth and thrombin generation in children after HSCT. Materials and methods. Ten patients (1-17 y. o.) were investigated before and 1 hour after platelet transfusion. Eight out of ten patients were given 100 ME/kg/h heparin. Concentrate was prepared by apheresis, y-irradiated (25 Gy), leukofiltrated and stored for 3-5 days before the transfusion. Mean concentrate dose was 6.5 ± 5.4 ml/kg. Platelet count was performed in whole blood and platelet rich plasma (PRP) before and after the transfusion. Platelet a-granules and dense granules secretion markers (CD62P and Mepacrine), non-activated and activated form of the glycoprotein GPIIb/IIIa (CD61 and PAC-1), glycoprotein GPI (CD42b) and PS (annexin V) expression were measured by flow cytometry. The integral estimation of haemostasis state was performed with pre-production model of Thrombodynamics-4D Analyser System (HemaCore Labs). Coagulation was activated by immobilized tissue factor (TF) in PRP. Spatial clot growth was registered by light scattering. Thrombin generation in space and time was determined using the registration of the UV-LED excited fluorescence of thrombin-activated 7-amino-4-methylcoumarin (AMC) substrate.
Results. Platelet count in PRP showed significant effect of transfusion (means±SD before/after the transfusion: 8.0 ± 6.6/52.3 ± 25.2 x 10^3/pl, p less then 0.001). However, the platelet functional activity assay showed reduced platelet activity per single platelet both before and after the transfusion: secretion of dense granules (Mepacrine index 1.37 ± 0.44/1.35 ± 0.19, reference interval 2.3-3.4), a-granules (CD62P 6713 ± 2388/5968 ± 2159 a.u., reference interval 9750-12 300 a.u.) and expression of non-activated GPIIb/IIIa (CD61 3179 ± 1468/3290 ± 715 a.u., reference interval 4000-7800 a.u.) stayed depressed after transfusion and did not change significantly. PS expression was normal before and after the transfusion (Annexin V 0.4-14.0/4.3-40.0 %, reference interval 0,8-38,1 %). The estimation of haemostasis state with Thrombodynamics-4D assay showed the change in spatio-temporal distribution of thrombin. It changed from diffuse to front-shaped after the transfusion, though did not reach wave-shaped distribution with distinguishable peaks, observed in plasma of healthy volunteers. The assay revealed a significant increase of clot growth rate V (25.4 ± 7.7/32.5 ± 3.9 pm/min, P = 0.004, reference interval 34-40 pm/min) and produced amount of AMC (122 ± 48/207 ± 35 pM*mm, p less then 0.001, reference interval 180-320 pM*mm), associated with amount of thrombin. Conclusion. The functional activity of platelets is reduced in patients after HSCT and stays reduced after the platelet transfusion. However, due to the significant increase in platelet count, the transfusion integrally leads to normalization of clotting, although the clot growth and thrombin propagation parameters do not reach such of healthy volunteers. The study was supported by the RFBR grants 15-34-70014, 15-54-45036 and 14-04-00670.
ABSTRACT NO.: P-198
Experience of treatment of chronic graft-versus-host disease using the method of extracorporeal photopheresis
L. Hushchina, N. Kirsanova, G. Mareika, N. Minakovskaya, D. Prudnikov, A. Alexeychik
National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus
Key words: chronic graft-versus-host disease, alloHSCT, ECP
Introduction. Chronic graft-versus-host disease (cGVHD) is the most serious and common complication of alloHSCT, it occurs in 30 % to 60 % of patients. cGVHD represents the major
cause of non-relapse mortality and late morbidity in transplant survivors.
Aim. The aim of our study was to assess the efficacy of extracorporeal photopheresis (ECP) in cGVHD.
Materials and methods. Patients and methods: 9 pts (5 female, 4 male), age from 2 to 24 y.o. (median 11 y.o.) suffering from ALL - 3 pts, AML - 2 pts, ABL - 1 pt, CML - 1 pt, thalassemia - 1pt, chronic granulomatous disease - 1 pt. All pts received allo-HSCT: matched unrelated HSCT - 2 pts (22 %), mismatched unrelated HSCT - 1 pt (11 %), matched related HSCT - 5 pts (56 %), haploHSCT - 1 pt (11 %). Onset type of cGVHD is progressive (persistent signs and symptoms of aGVHD) - 7 pts (78 %), quiescent (no clinical signs or symptoms of aGVHD) - 1 pt (11 %), denovo (no prior history aGVHD) - 1 pt (11 %). Frequency of organ involvement: skin - 9 pts (100 %), joints - 1 pt (11 %), liver - 2 pts (22 %), oral mucosa- 4 pts (44 %), gastrointestinal - 1 pt (11 %), genitalia - 1 pt (11 %), eyes - 1 pt (11 %), lung - 1 pt (11 %). ECP were used as second or third line therapy. Fourpatients received only ECPas immunosupressivetherapy, 5 pts continued to receive steroid and ECP. Corticosteroid status is dependent - 1 pt from 5, refractory - 4/5 pts. Patients received ECP twice weekly during first 2 weeks, then 1 times per week during 1 month and after once monthly. Patients received 2 to 21 cycles of ECP (median 10 cycles). Median time of carrying out ECP is 12.8 month (from 4.1 to 87.2 month) from HSCT date.
Results. Complete resolution (CR) was achieved in 2 pts (22 %), partial resolution (PR) - in 6 pts (67 %); absence of response was in 1 pt (11 %). Steroid therapy could be discontinued in 4 from 5 pts (80 %) (1 pt with CR, 3 pts with PR), decrease in steroid dosage with PR of GVHD clinical signs - 1 pt (20 %). No patients had sideeffects during or immediately after the procedure ECP.
Conclusion. Our results indicate that ECP is effective method for treatment of chronic GVHD and allows completely withdrawal steroid therapy in most patients.
ABSTRACT NO.: P-200
The acute form of "graft versus host diseases" in children: prognostic factors and treatment of mesenchymal stem cells steroidrefractory form
N. Minakovskaya
National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus Key words: graft versus host diseases, allogeneic hematopoietic stem cell transplantation, mesenchymal stem cells
Introduction. Steroidrefractory forms of acute "graft versus host diseases" in children after allogeneic hematopoietic stem cell transplantation oneof the main causes of therapy-related death.
Aim. Is to improve the treatment steroidrefractory forms of acute "graft versus host diseases" in children with hematologic malignancies and primary immunodeficiency after allogeneic hematopoietic stem cell transplantation by detection of risk factors and transplantation of mesenchymal stem cells.
Materials and methods. The study included 218 SCT to 214 children (age 6 months - 18 years, mediana 10.5 y.o.) in the period from 1998 to 2014 . The largest number of SCT performed to children with acute leukemia (ALL - 72 (33 %), AML - 41 (18.8 %)) and SAA - 45 (20.6 %). 20 patients with steroidrefractory aGvHD for treatment was carried mesenchymal stem cells (MSC) and 11 patients without MSC constituted the control group. All patients and control groups were matched for age and sex. Results. The incidence of acute GVHD in children after SCT found in 120 (55 %) cases of 218 transplants. Factors affecting the development of life-threatening III-IV stages steroidrefractory acute GVHD are incompatibility antigens HLA-system - 13 (65 %, P=0.035), donor age older than 30 years - 17 (65.4 %, P=0.0268) and unrelated allogeneic HLA-incompatible HSCT - 11 (78.5 %, p=0.0266). Number of TNC in the graft a 5.0 x 10Ykg body weight of the recipient is a risk factor for stage IV steroidrefractory acute GVHD - 9 (32.1 %). Conclusion. Carrying allogeneic transplantation of MSC led to a complete and partial remission of steroidrefractory acute GVHD in 16 (80 %) of the 20 patients, in the control group partial remission occurred in 3 (27 %) patients.
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ABSTRACT NO.: O-225
Survival and treatment of children with acute graft versus host disease: an 8-year single-сentre experience
A. Kozlov, T. Bykova, Yu. Fedukova, M. Kucher, E. Morozova, E. Semenova, A. Borovkova, K. Ekushov, S. Bondarenko, O. Slesarchuk, I. Kulagina, E. Babenko, A. Alyansky, M. Estrina, L. Zubarovskaya, B. Afanasyev
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Russia
Key words: acute graft versus host disease, methylprednisolone, steroid-refractory, extracorporeal photopheresis, anticytokine therapy
Introduction. Despite remarkable progress in the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT) the rate of transplant-related mortality remains high due to severe transplant-associated complications and acute graft host disease (aGVHD) is among the most frequent and life-threatening.
Aim. Evaluation of the overall survival (OS) in children with aGVHD that were treated with methylprednisolone (MEP) as first-line therapy and extracorporeal photopheresis, anticytokine therapy or alemtuzumab as second line therapy.
Materials and methods. A total of 97 children (range 1-18 years) with aGVHD grade II-IV after allo-HSCT were included in the study. In all cases the first line therapy consisted of 1-2 mg/kg of methylprednisolone (MEP). Response was evaluated 3 days after therapy initiation. If there was no response after 3 days of steroids or if aGVHD flared during the corticosteroid taper, then steroid-refractory aGVHD was diagnosed. Extracorporeal photopheresis (ECP) was used as further therapy in 31 (48 %) patients, anticytokine therapy was used in 29 children (45.5 %) (etanercept (n = 12), infliximab (n = 9), daclizumab (n = 8)) and alemtuzumab in 4 (6.5 %). Both groups (responders and non-responders to MEP) were homogenous in terms of such characteristics as median age (8 years vs 8.5 years), sex (female 41 % vs 39 %), diagnosis (acute leukemia 73 % vs. 69 %), donor type (unrelated donors 75 % vs 67 %, P=0.8), transplant source (bone marrow 67 % vs 63 %) and conditioning regimen (myeloablative 36 % vs 45 %, P=0.2), respectively. Nevertheless, these groups (responders and non-responders to MEP) were heterogeneous in terms of aGVHD stage (severe 24 % vs 59 %, P = 0.03), respectively. Overall survival was estimated by the means of Kaplan-Meier analysis and comparison of two survival curves was done by the means of log-rank test.
Results. Five-year overall survival (OS) of patients included in the study was 48.6 %. Median follow-up was 20.5 moths (range 6-124). Complete response to MEP was registered in 33 (34 %) patients and inadequate response in 64 (66 %) patients. Complete responders didn't require any further immunosuppression and MEP could be successfully discontinued, meanwhile non-responders required additional immunosuppressive treatment options. Patients with steroid-sensitive course of aGVHD demonstrated 5-year OS of 69 % and children with steroid-refractory aGVHD showed 5-year OS of 39 % (P = 0.08). Overall response to the second-line therapy was 68 % after ECP (complete response - 32 %, partial response - 36 %) and 70 % after anticytokine therapy (complete response - 42 %, partial response - 28 %), P=0.77. Among 4 patients with alemtuzumab 2 complete responses and 1 partial response were registered. Children that responded to second-line therapy of aGVHD demonstrated 5-year OS of 54 % which didn't statistically differ from OS of steroid-sensitive group (P=0.33). Conclusion. Prognosis of children with steroid-refractory aGVHD still is less favorable than in steroid-sensitive group despite administration of such modern treatment options as ECP and anticytokine therapy. Prognosis of children that respond to second line therapy of aGVHD is comparable to prognosis in steroid-sensitive aGVHD.
ABSTRACT NO.: 0-227
Invasive fungal diseases in adolescents and young adults after allogeneic hematopoietic
stem cell transplantation
M. Popova1, A. Volkova1, O. Ayzsilnieks1, O. Pinegina1, S. Ignatyeva2, K. Ekushov1, O. Slesarchuk1, M. Vladovskaya1, L. Zubarovskaya1, N. Klimko2, B. Afanasyev1
O 1First Pavlov State Medical University of St. Petersburg, Russia;
h^ 2North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia
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Key words: IFD, allo-HSCT, adolescents and young adults, epidemiology, IA
Introduction. Invasive fungal diseases (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still actual problem despite improving prognosis recently. Data of IFD in adolescents and young adults after allo-HSCT are limited. Aim. This study focuses on epidemiology of IFD in adolescents and young adults after allo-HSCT.
Materials and methods. In retrospective single-center study from Jan 2013 to Dec 2014 were included 80 pts after first allo-HSCT. The median age was 20 y.o.(15-25). Underlying diseases were acute leukemia - 71.5 %, lymphoma - 15 %, not malignant diseases - 7.5 %, other - 6 %. Allo-HSCT from MUD was performed in 67 %, MRD - 24 %, haplo - 9 %. RIC were used in 72.5 %. EORTC/MSG 2008 criteria for IFD diagnosis were used, probable and proven IFD were taken into analysis. Active diagnostic strategy: bronchoscopy with BAL in pts with CT-scan lung lesions before HSCT was used. "Active IFD"means IFD diagnosed just before allo-HSCT. IFD-events mean new IFD and relapse of IFD in pts who had it before allo-HSCT. Results. IFD was diagnosed before allo-HSCT in 19 % pts: invasive aspergillosis (IA) - 11 pts, hepatosplenic candidiasis (HSC) - 3 pts, and one patient had two IFD (IA+HSC). Complete response to antifungal therapy was in 40 % pts, partial response - 26,7 %, and "active IFD"- 33,3 %. Secondary antifungal prophylaxis was made with voriconazole (80 %). Pts without IFD before allo-HSCT (n = 65) received primary prophylaxis with fluconazole - 85 %. Cumulative incidence of IFD-events at 2 years after allo-HSCT was 19 %: 14 cases of new IFD and one relapse of IA. Median time to IFD-event onset was D+43 (14-577). Incidence of IA was 15% with median time to onset D+27.5 (14-577), IC - 2.5 % with median time to onset D+226.5 (54-399), pneumocystis pneumonia (PCP) - 1.25 %, day of onset - 43. The main sites of infection were lungs - 86.7 %. Risk factors for IFD after allo-HSCT in pts without IFD before HSCT were ageless 18 y.o. (P=0.03), not malignant underlying disease (P=0.003), active underlying disease at the moment of HSCT (P=0.01), neutropenia (grade 4) more 20 days (P=0.004), and acute GvHD (P=0.008). Seven pts (58.3 %) with IA were treated with voriconazole as a first line treatment, all pts with IC - ehcinocandins, and patient with PCP was treated with trimethoprim-sulfamethoxazole. 12-weeks overall survival (OS) from day of IFD diagnosis after allo-HSCT was 93.3 %. 12-weeks OS in pts with
IA was - 91.7 %, two pts with IC and one patient with PCP were alive at 12 weeks after IFD diagnosed. Voriconazole as a first line treatment improved 12-weeks OS in pts with IA after allo-HSCT (100 % vs 80 %, P=0.2). 100-days OS after allo-HSCT was 85 %, 2-year OS after allo-HSCT was 67.5 %. There was no statistical difference in 2-year OS in pts with (53.3 %) or without IFD (70.8 %) before allo-HSCT (P = 0.3).
Conclusion. Incidence of IFD in adolescents and young adults before allo-HSCT was 19 %. Cumulative incidence of IFD at 2 years after allo-HSCT was 19 %. The main IFD was IA - 80 %. Risk factors for IFD after allo-HSCT were ageless 18 y.o., not malignant underlying disease, active underlying disease at the moment of HSCT, neutropenia (grade 4) more 20 days, and acute GvHD. 12-weeks OS from IFD diagnosis after allo-HSCT was 93.3 %. IFD before and after allo-HSCT did not impair the outcome of the transplantation in adolescents and young adults with effective diagnosis, treatment and secondary prophylaxis have been used.
ABSTRACT NO.: P-252
New HLA-haplotypes as the result of crossover
V. Zakharova, O. Shragina
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia Key words: HLA, MHC, crossover, double crossover, PCR, SSP, sequence based typing
Introduction. Of all the genetic and non genetic factors that can influence stem cell transplant outcome, the most important is HLA matching. A most striking feature of the HLA system besides its many closely linked, functionally related and highly polymorphic genes is the significant over- and underrepresentation of certain allelic combinations, called linkage disequilibrium.
In rare cases, the HLA genes can be separated by genetic recombination (i.e. crossover of genetic material between homologous chromosomes during meiotic division). This recombination occurs quite rarely as established from testing large numbers of famylies. Recombination is evident when family typing studies are performed and greatly complicate the search for a marrow donor.
Aim. HLA-typing for searching of related donor for hematopoetic stem cell transplantation.
Materials and methods. One patient with acute myeloid leukemia (AML) and one patient with unknown diagnosis and family members (two parents and one sibling in each family) were included in the study.
HLA-typing low and high resolution for loci HLA-A*, B*, C*, DRB1*, DQB1* was performed by PCR-SSP (Sequence-specific primer, Invitrogen, USA) and SBT (Sequence-based typing, Invitrogen, USA).
Results. HLA typing showed double crossover in family 1 and single crossover in family 2. Father's haplotypes in patients and siblings are not shown. Family 1:
[patient: A*03, C*06, B*57, DRB1*04, DQB1*03:01]; [sibling: A*24, C*06, B*57, DRB1*07, DQB1*03:03];
[mother: A*24, C*06, B*57, DRB1*07, DQB1*03:03 / A*03, C*07, B*07, DRB1*04, DQB1*03:01]. Family 2:
[patient: A*03, C*04, B*35, DRB1*01, DQB1*05]; [sibling: A*03, C*04, B*35, DRB1*15, DQB1*06];
[mother: A*03, C*04, B*35, DRB1*01, DQB1*05 / A*01, C*07, B*07, DRB1*15, DQB1*06].
Case in family 1 shows a double recombination between the HLA-A/HLA-C and HLA-B/HLA-DRB1 loci. Case in family 2 illustrate a recombination between the HLA-B and HLA-DRB1 locus. Based on linkage disequilibrium and haplotype frequencies it is likely that recombinant haplotype is present in proband rather then sibling in family 1 and present in sibling rather then proband in family 2.
Conclusion. Althgouh crossover in HLA genes is a rare event, this cases illustrate that such recombination in hot spots resulted in mismatch between the patient and potential donor. Even if siblings are matching it is also useful to determine the HLA haplotypes of the parents if possible. In cases similar to described above grandparents, cousins, aunts and uncles should be typed to get exact distribution of haplotypes.
ABSTRACT NO.: P-257
The safety of hematopoietic stem cell apheresis in children with oncological diseases
with body weight up to 15 kg
I.B. Kumukova, P.E. Trakhtman, E.Ye. Kurnikova
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
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Key words: hematopoietic stem cell apheresis
Introduction. Hematopoietic stem cell (HSC) apheresis in children with low body weight is associated with a number of technical difficulties and safety problems: vascular access, a risk of hypervolemia and hypothermia, the emerging necessity of large volume leukapheresis (LVL), a risk of citrate toxicity and its underestimation, patients'sedation in some cases. Aim. The analysis of the experience of HSC apheresis in children with oncological diseases and body weight up to 15 kg.
Materials and methods. Overall, 77 HSC aphereses were performed in 76 patients. The analysis did not include 1 repeat apheresis. The median age comprised 33.7 (6-84) months, the median body weight - 12.6 (6-15.8) kg. The nosological structure: neuroblastoma (n = 66), medulloblastoma (n = 4), nephroblastoma (n = 2), Ewing sarcoma (n = 2),
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yolk sac tumor (n = 1), pleuropulmonary blastoma (n = 1). HSC mobilization - granulocyte colony-stimulating factor 10-20 mg/kg/d for 3-7 days with the use of plerixafor if needed. The HSC apheresis procedure was conducted using COBE Spectra system (n = 9) or Spectra Optia (n = 68), with the preliminary filling of erythrocyte-containing blood components with donor erythrocyte suspension in 68 cases out of 76. HSC aphereses in 5 children less than 10 months old with body weight less than 9 kg were carried out at intensive care unit under constant monitoring and sedation and with prophylactic administration of calcium gluconate. Other procedures were performed at Transfusion Department without intensive monitoring and calcium gluconate administration.
Results. Only 1 patient out of 76 needed a repeat apheresis to achieve optimal CD34+ levels. In 8 patients, HSC apheresis was performed via the previously implanted two-channel central venous catheter (CVC); 8 patients had a replacement of a one-channel subclavian CVC by a two-channel one (Hickman 7F or Certofix 5F). 60 patients needed an implantation of a temporary CVC with femoral access. 11 patients out of these 60 had mild catheterization complications such as repeat venepunctures or haemotomas at puncture sites. In 1 case, the internal jugular vein was damaged during a subclavian vein catheterization attempt wherefore apheresis was postponed for 1 month. The median apheresis duration was 289 (156-444) min. The median circulating blood volume processed per a procedure was 2.85 (1.5-5.2). The characteristics of apheresis products: the median NC/kg- 12 x 158/kg (2.29 x 108/kg - 30.14 x 108/kg), the median CD34+ - 13.83 x 106/kg (2.37 x 106/kg - 63.37 x 106/kg). In 35 cases out of 76, LVL was carried out, and only in 1 case there was a mild citrate reaction. In 8 patients older than 4 years of age with body weight ranging from 14.5 to 15.8 kg and hemoglobin levels higher than 115 g/l, contour filling with erythrocyte suspension was not performed. There were no complications associated with anaemia, hupovolaemia, transfusions. The median thrombocyte level after apheresis comprised 109 x 109/l (38-311 x 109/l). A decrease in hematocrit levels after apheresis was registered in 4 children.
Conclusion. HSC apheresis in younger children requires additional efforts and particular attention as well as a high level of competence of the personnel. In case of an adequate preparation for apheresis, the procedure seems to be quite safe and, in the majority of cases, does not require intensive monitoring and intervention. There were no grave complications of apheresis registered. Thrombocytopenia and a decrease in hemoglobin levels after apheresis were not threatening. LVL does not increase the risk of complications as compared with the standard HSC apheresis. According to the results of our study, the majority of complications in young children are associated with the need for an adequate vascular access - the implantation of an additional CVC.
ABSTRACT NO.: OP-258
The role of bronchoscopy in the diagnosis of invasive pulmonary mycosis in children after allogeneic hematopoietic stem cells transplantation
A. Volkova1, M. Popova1, K. Ekushov1, T. Bogomolova2, S. Ignatyeva2, B. Smirnov3, L. Zubarovskaya1, B. Afanasyev1, N. Klimko2
'First Pavlov State Medical University of St. Petersburg, Russia; 2North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia;3Saint-Petersburg Electrotechnical University "LETI", Russia
Key words: invasive pulmonary mycoses, bronchoscopy
Introduction. Early diagnosis of invasive pulmonary mycoses (IPM) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the factors positively influencing the survival.
Aim. The role of bronchoscopy in early diagnosis of IPM in children after HSCT is not clear.
Materials and methods. In prospective single-center study in 2009 to 2014 yy we evaluated the safety and efficacy of bronchoscopy (n = 209) with bronchoalveolar lavage (BAL) for the diagnosis of IPM in 135 children after allo-HSCT. The median of age was 12 (from 1 to 18) years old. In a specialized endoscopy room or ICU (13 %) bronchoscopy was made with EVIS EXERA II Olympus endoscopic video system with an external diameter of the distal end tubes of the 3.6 mm and 4.9 mm. Different methods of anesthesia were performed, depending on the age and the degree of respiratory failure of patients with mandatory monitoring of vital functions and oxygen levels. The obtained samples were sent to the lab for microscopy with white calcofluor, culture, and galactomannan (GM) test (Platelia Asregillus, Bio-Rad). In 4 (3 %) patients there were signs of endobronchial fungal growth, and we performed biopsy during bronchoscopy. Two (1.5 %) patients with negative BAL underwent percutaneous automatic biopsy and lung lobectomy for diagnosis of IPM. EORTC/MSG 2008 criteria for IFD diagnosis were used, only "probable" and "proven" IFD were taken into analysis.
Results. No major complications occurred during bronchoscopy. IPM was found in 41 % patients with lesions on CT scan. 89 % IPM were "probable" and 11 % "proven" according to EORTC/MCG 2008 criteria. The results of GM tests in BAL fluid were positive in 66 % samples. Culture and microscopy were positive in 43 % cases. Main pathogens were Aspergillus spp. (73 %) and mucormycetes (14 %). Rare pathogens were Acremonium spp., Paecilomyces spp., Fusarium spp., Alternaria spp. and Pjirovecii. Two or more pathogens were detected in 9 %. In multivariate analysis, galactomannan assay in BAL fluid showed a higher sensitivity compared to microscopy and culture (83.3 % and 46.3 %, respectively). Conclusion. In children after allo-HSCT bronchoscopy with modern video endoscopy equipment and adequate anesthetic is effective and safe method of diagnosis of invasive pulmonary mycoses.
Detection of galactomannan in BAL is more effective than microscopy and culture for diagnosis of invasive aspergillosis in in children after HSCT.
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ABSTRACT NO.: OP-261
The related factors of influencing unrelated umbilical blood transplantation on children with Wiskott-Aldrich syndrome
Xin-ni Bian, Pei-fang Xiao, Jun, Shaoyan Hu
Children's Hospital of Soochow University
Key words: Wiskott-Aldrich syndrome (WAS), unrelated cord blood transplantation (UCBT), granulocyte engraftment, platelet engraftment, HLA high resolution, nutritional status Introduction. More and more infants with Wiskott-Aldrich syndrome (WAS) have been recently diagnosed with WAS gene sequencing available in China. It has been accepted that hematologic stem cell transplantation (HSCT) is one of the most curable treatment. A few institutions preferred well matched unrelated peripheral blood stem cell transplantation (PBSCT) on WAS patients in China. However, patients with WAS faced two problems: one is well matched unrelated donor is difficult to find in the Chinese bone marrow bank, another is unrelated donor refuse donate stem cells after selected as a donor. As a result, many infants have to wait for suitable donor at the risk of increasing bleeding, serious infection, even death. So unrelated cord blood is a perfect option for such patients.
Aim. To explore the outcome unrelated donor cord blood transplantation (UCBT) on children with Wiskott-Aldrich syndrome (WAS) and impacting factors, such as HLA high resolution, nutritional status, virus infection.
Materials and methods. From February to September of 2015 five patients diagnosed as WAS were treated with UCBT in our center. The factors as the nutritional status prior to transplantation, age of transplantation, HLA matched degree, post-transplantation graft versus host disease (GVHD), infection status were analyzed. Follow-up lasted to January 2016. Conditional regimen include Busulfan at 1.0 mg/kg.q6h for 4 days, Fludarabine 40 mg/m2.d for 4 days, Cyclophosphamide 60 mg/kg.d for 2 days and ATG 2.5 mg/kg.d for 3 days. GVHD prevention consists of MMF at 20 mg/kg.d and Cyclosporine at 3 mg/kg.d.
Results. According to the STR results, five children with WAS were cured with UCBT. Granulocyte engraftment was 15 days, 12 days, 11 days,14 days and 15 days, respectively. Platelet engraftment was 39 days, 16 days, 17 days, 34 days and 36 days, respectively. HLA high resolution matched between receipt and donor was 8/10, 10/10, 5/10, 10/10, 10/10, respectively. Three of the patients suffering CMV viremia before transplantation showed a platelet engraftment delay. One case with severe malnutrition showed severe GVHD of skin and intestine and recurrentsevere infections after transplantation. Follow-up 4 months to 12 months, 5 cases keep a stable value of STR at 100 %.
Conclusion. CMV viremia and nutritional status before transplantation influenced the platelet engraftment and complications of UCBT. The degree of HLA high resolution has no relations with the engraftment of neutrophil and platelet and complications of UCBT.
ABSTRACT NO.: PP-275
Second haploidentical stem cell transplantation as a salvage therapy for children with acute leukemia relapsed after first allo-HSCT
P. Kozhokar, O. Paina, A. Borovkova, E. Semenova, A. Rats, S. Razumova, K. Ekushov, Yu. Fedukova, O. Slesarchuk, L. Zubarovskaya, B. Afanasyev
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Russia
Key words: acute leukemia, allogeneic HSCT in children, relapse, second haploidentical HSCT
Introduction. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for acute leukemia. However post-HSCT relapse remains an important cause of treatment failure with relapse rates ranging from 30 % to 70 %. Optimal treatment of relapse after HSCT remains unclear.One of possible options might be second transplantation from another donor.
Aim. The aim of study was to evaluate the efficiency of second haploidentical HSCT from haploidentical donor for treatment of relapse of acute leukemia after first allogeneic HSCT in children
Materials and methods. We retrospectively analyzed outcomes of 21 second haploidentical HSCT performed in our Institute for children with acute leukemia (AML - 6, ALL - 14, mixed lineage leukemia-1), relapsed after the first HSCT. Median age at the time of first HSCT - 5 y.o. (13 m.o. - 17 y.o.), median age at second HSCT - 6 y.o. (22 m.o. - 17 y.o.). Donor for the first HSCT were matched unrelated (n = 7), matched related (n = 6), haploidentical (n = 6), singeneic (n = 1). The median time from first to second allo-HSCT - 9 months (34 days - 28 months). In case of first haploidentical donor second HSCT were from another donors. Cytoreductive therapy prior to second HSCT was performed in 19 pts. There was no response in 16 pts, 1 pt achieved complete remission and 4 pts were transplanted in aplasia. The conditioning regimen for second HSCT was myeloablative in 4 pts (conventional - 2, reduced toxicity - 2), reduced intensity - 17 pts.
Results. 19/21 patients achieved engraftment, median of neutrophyl engraftment - 20 days (12-34 days). At the time of analysis 10 pts are alive with median follow up of 5 months (2 months - 88 months).Five - years overall survival (OS) - 42.5 %. The period between the first to second HSCT had no statistically effect on OS. Relapse rate after second allo-HSCT was 42 %. Non relapse mortality - 21 %.The causes of death were relapse or progression of disease (7 pts), acute GvHD (3 pts), infectious complications (1 pt). Conclusion. Our data showed that the second haplo-HSCT is acceptable choice for treatment children with acute leukemia relapsed after first allo-HSCT. Further trials are needed to define the role of second haplo - HSCT including combination with additional treatment after transplantation.
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SIOP ASIA CONGRESS
ABSTRACT NO.: O-279
Cytomegalovirus retinitis in hematopoetic stem cell pediatric transplant patients
B.S. Pershin, O.A. Boginskaya, A.B. Smirnova
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: cytomegalovirus retinitis
Introduction. Cytomegalovirus (CMV) retinitis is associated with immunosupression and can cause irreversible vision loss Aim. A clinical case of a patient 5 y.o. with Wiskott-Aldrich syndrome.
Materials and methods. Stem cell transplantantion (SCT) was performed from an unrelated donor transplant with processing TCRaR/CD19-deletion. Ocular examination before SCT didn't reveal any pathology, visual acuity (VA) was 20/20.
Results. On 11 day after SCT CMV viremia was 1386 copies/ml and decreased on 14 day to 500 copies/ml. The negative results confirming CMV absence were achieved on 16 day after BMT under essential supplement of intravenous Ganciclovir.
Ophthalmic exam on 45 day after SCT revealed a single white crescent formed focus with blurring edges in macular area, measured as 1.5 of optic disc diameter. VA of the left eye deteriorated to 20/63. Three intravitreal injections of Ganciclovir 2 mg/0.1 ml were performed once a week.
With each implemented procedure the described focus became more transparent. After third injection it was absolutely eliminated. Previously involved retina appeared to be unaffected with exceptionally thin line of retinal pigment epithelium dispersion on the periphery of macular area. VA improved to 20/20
Conclusion. Due to the difficulties in defining VA in infants and toddlers it is important to remember that CMV retinitis may be asymptomatic. Regular ophthalmological monitoring in children after SCT is crucial. Early performance of intravitreal injections of specific antiviral agents allows to prevent spreading of inflammatory process in retina and maintain visual functions.
ABSTRACT NO.: OP-285
The role of bone marrow stromal cells functional characteristics in post-transplant hematopoietic reconstitution
N. Tsvetkov, I. Barkhatov, A. Shakirova, D. Romaniuk, A. Potter, L. Zubarovskaya, B. Afanasyev
First Pavlov State Medical University of St. Petersburg, Russia
Key words: hematopoietic stem cell transplantation, bone marrow stromal cells, hematopoietic reconstitution
Introduction. The role of the stromal microenvironment in hematopoietic stem cell transplantation (HSCT) is based on nonlineage-specific effects on proliferation and differentiation of HSCs. Deficient graft functioning observed in some cases necessitates development of functional tests for the stromal cells, in order to provide clinical indications for co-transplanting of hematopoietic and bone marrow stromal cells (BMSC), and evaluable introduction of alternative therapeutic approaches.
Aim. The aim of this study was to investigate the role of bone marrow stromal cells in the course of donor marrow cells engraftment and their significance in post-transplant complications.
Materials and methods. The study included clinical observation of the post-transplant course in ten patients with acute myeloid leukemia (AML) and 7 healthy donors. Bone marrow nucleated cells were selectively harvested two weeks prior to BMT, followed by monolayer culture in alpha-MEM culture medium with 20 % fetal bovine serum. Upon growth of fibroblast-like cell colonies (CFU-F), their hematopoiesis-supporting activity was determined in the agar-drop/liquid culture system, as well as their differentiating ability along adipogenic and osteogenic pathways. We have also analyzed the relative expression of selectin and CXCR4 genes in these cells.
Results. When comparing functional characteristics of BMSC from healthy donors and AML patients, an increased hemostimulatory activity of the latter was noted, as reflected by an increase in large and small CFU-GM numbers (p y correlated with platelet recovery time (P=0.05). In contrast, higher numbers of osteogenic colonies in culture were associated with an increased time to leukocyte lineage recovery (P=0.05). When analyzing gene expression in BMSC population, a decreased expression of the CXCR4 gene responsible for the homing < effect, with age of the patient's (P=0.05) was noted. The selectin gene expression in BMSC was higher by AML patients as compared to healthy donors.
Conclusion. Stromal cells derived from the patients' bone marrow exhibit higher proliferative activity and marked expression of molecules mediating HSC homing, as compared with a group of healthy donors. That finding could be explained by affection of stromal cells by previous chemotherapy and myelosuppression. BMSC from AML patients taken before bone marrow transplantation are characterized by a more pronounced capacity to osteogenic and adipogenic differentiation than those from healthy donors. Increased adipogenic differentiation ability of the BMSCs is associated with a more rapid recovery of hematopoiesis.
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ASTRACT NO.: O-296
Feasibility and outcome of allogeneic hematopoietic stem cell transplantation with post-transplant cyclophosphamide in children with acute leukemia. Single centre experience
O.V. Paina, A.S. Borovkova, P.V. Kozhokar, S.V. Razumova, K.A. Ekushov, O.A. Slesarchuk, I.S. Moiseev, O.V. Pirogova, A.L. Alyanskiy, E.V. Babenko, L.S. Zubarovskaya, B.V. Afanasyev
First Pavlov State Medical University of St. Petersburg, Russia
Key words: post-transplant cyclophosphamide in children, allo-HSCT
Introduction. Allogeneic hematopoietic stem cell transplantation from matched related, unrelated or haploidentical (allo-HSCT) donors (MRD, MUD, HaploD) are often the only method of radical treatment of patients suffering from hematological malignancies. The development of severe graft-versus-host (acute and chronic) disease (aGVHD; cGVHD) determines the length of hospitalization and significantly contributes to the structure of mortality, despite the use of new modes of conditioning regimens and modern pharmacological drugs (calcineurin inhibitors (CNI): cyclosporin A - CSA, tacrolimus - Tacro; m-TOR inhibitors - Sirolimus - Sir). At the present time the John Hopkins and Fred Hutchinson Cancer Research Center groups evaluate the efficacy of high dose (50 mg/kg) cyclophosphamide administered on day 3 and 4 (PTCY) after allo-HSCT as a new option and have obtained the current satisfactory results in adults, but its feasibility is not clear in children.
Aim. In the current study, we retrospectively evaluated the feasibility and outcome of PTCY based allo-HSCT (MRD-HSCT, MUD-HSCT and Haplo-HSCT) in children with acute leukemia employing chemotherapy based conditioning regimen (MAC and RIC). Primary end points: engraftment rate, aGVHD, overall survival (OS). Secondary end points: relapse rate, non-relapse mortality (NRM).
Materials and methods. 132 children (range from 0-19 y.o., median 8 y.o.) with AL (ALL - 78 pts, AML - 52 pts, JMML - 2 pts) were included. PTCY-group - 84 pts 1st or 2nd remission - 33 pts, resistant disease - 50 pts). Types of HSCT: MRD-HSCT - 1 pts, MUD-HSCT - 25 pts, Haplo-HSCT - 57 pts. Conventional prophylaxis of GVHD (control-group) - 49 pts (1st or 2nd remission - 15 pts, resistant disease - 34 pts), types of HSCT: MRD-HSCT - 4 pts, MUD-HSCT - 6pts, Haplo-HSCT - 39 pts). Conditioning regimen: MAC + ATG received 29 pts, MAC + PTCy 50 mg/kg on D+3, +4 in 36 pts. RIC + ATG received 20 pts, RIC + PTCy 50 mg/kg on D+3, +4 in 47 pts. All pts PTCy-group had prophylaxis of aGVHD based on calcineurin inhibitors (CSA or Tacro) with or without MMF or Sir since D+5. The control group had prophylaxis of aGVHD by CNI as well with MMF and methotrexate - 49 pts. The median follow-up of surviving patients was 13.5 months. Statistical analyses were performed using SPSS V19.
Results. 73.5 % of patients achieved engraftment in PTCY-group vs 81.6 % control-group (P = 0.4). Cumulative incidences of aGVHD grate II-IV (19.7 % vs 6 %, P = 0.000) was significantly lower in PTCY-group compared to control-group. Cumulative incidence of relapse (44.5 % vs 50 %, P=0.7), NRM (14.8 % vs 25 %, P = n.s.) were not statistical significant. One-year overall survival was the same in both group (PTCy-group - 54.2 % vs 53.1% in control-group, P=0.5).
Conclusion. Allo-HSCT with PTCY in acute leukemia is a safety and feasibility option. PTCY in combination with CNI and MMF or sirolimus had lower incidence of aGVHD. Future studies are needed to increase OS and reduce relapse rate in post-transplant period.
ABSTRACT NO.: PP-327
High mixed chimerism in CD3 cell line in patients with AML after allogenic HSCT
V. Brilliantova, L. Shelikhova, Zh. Shekhovtsova, E. Gutovskaya, I. Shipitsina, D. Shasheleva, D. Balashov, A. Livshits, R. Khismatullina, M. Persiantseva, M. Ilushina, E. Raikina, V. Bobrynina, M. Maschan, A. Maschan
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: chimerism, acute myeloid leukemia, CD3+ cells
Introduction. Hematopoethic stem cells transplantation (HSCT) is the only way to save a life in patients with many diseases, especially in onkohematology. The most common complications after HSCT are infections, allograft rejection, graft-versus-host-disease (GVHD) or relapse of disease. To observe the process of transplant functions measuring of donor's chimerism (a number of donor's cells) in peripheral blood and bone marrow is often used in patients received allogenic HSCT. After HSCT with TCRab depletion a long-term high mixed chimerism may observed in some patients in CD3 cell line. It is important to understand, how high mixed chimerism in CD3 cell line affects on post transplant period. Aim. Research study of donor's chimerism in CD3 cell line in patients with AML received allogenic HSCT <
Materials and methods. In this study was observed 27 patients with AML, received HSCT since May 2012 till October 2014. 11 patients received haploidentical transplantation and 16 patients receaved transplantation from HLA-matched unrelated donor. Measuring of donor's chimerism proceeds each 30 days during 1 year after HSCT. During this time 11 patients had a relapse. CD3 cells were isolated on dynabeads (applied biosystems) from bone marrow samples. Chimerism was detected by using Insertion/Deletion polymorphisms (RTQ PCR). Results. The research study of donor's chimerism in CD3 cell line has detect the group of patients with high mixed chimerism (recipient cells is more than 40 %). However, patients in this group that didn't have relapse all received HSCT from unrelated donor. In patients, received HSCT from haploidentical donor, number of recipient's cells more than 15 % in CD3 cell line was observed only in patients with relapse.
Conclusion. High mixed chimerism (more than 40 %) in CD3 cell line in patients with AML after HSCT from unrelated donor is not associated with relapse, comparing with patients received HSCT from haploidentical donor. Patients with haploidentical donor and more than 15 % of recipient's cells in CD3 cell line all had relapse.
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ABSTRACT NO.: PP-345
Breastfeeding is not contraindicated in patients undergoing HSCT
D. Skobeev1, E. Skorobogatova1, K. Kirgizov1, 2
1Russian Children's Clinical Hospital, Moscow, Russia; 2Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: Breastfeeding during, stem cell transplantation,post-transplant period.
Introduction. In spite of current conceptions and recommendations on children's nutrition with HSCT, the question about breastfeeding remains open and controversial for now. Aim. We aimed to show the possibility of breastfeeding during the HSCT for pediatric patients.
Materials and methods. 20 patients with HSCT at the BMT unit of the Russian children's clinical hospital were allowed to be breastfed between 2012 and 2015. The average age of the children was 18 months (between 7 and 30 months). Types of HSCT: Autologous 30 % (n = 6), Allogenic 70 % (n = 14): MUD 40 % (n = 8), MSD 15 % (n = 3), haploidentical 15 % (n = 3). All pts. after AutoHSCT were with neuroblastoma (30 % from all pts.) received conditioning regimen with Treo 42 gr/sq.m. + Melphalan 140 mg/sq.m. All patients with Allogenic HSCT received full intensity Treo-based conditioning regimen. Diagnosis: AML - 30 % (n = 6), Hurler syndrome - 20 % (n = 4), SCID - 15 % (n = 3), CGD - 5 % (n = 1). Breastfeeding was not terminated during the conditioning period and within the whole early post-transplant period with complications.
Results. The incidence of severe oropharyngeal mucositis and neutropenic enterocolitis (higher than grade 2) in all the survived patients (n = 20) was 15 %. There were no severe infectious complications and inoculation of de novo pathological microflora that serve as indicators of breastfeeding complications observed in the analysed group. The incidence of intestinal form of graft versus host disease (GvHD) with allogenic HSCT (more than II gr.) was 14.3 %.
Conclusion. The performed analysis demonstrated that breastfeeding may be recommended for children at the BMT unit as it doesn't affect the process of early post-transplant period and doesn't increase the incidence of toxic and immune complications, protected gastrointestinal infectious complications and is the important element of psychological support in the "mother-child" system in a clinical setting.
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ABSTRACT NO.: OP-348
Reduced-intensity versus myeloablative conditioning allogeneic hematopoietic stem cell transplantation for patients with Hurler syndrome
A. Borovkova1, K. Kirgizov2, E. Skorobogatova3, O. Paina1, P. Kozhokar1, S. Razumova1, Yu. Fedyukova1, E. Pristanskova3, N. Sidorova3, V. Konstantinova3, A. Osipova1, K. Ekushov1, E. Semenova1, L. Zubarovskaya1, A. Maschan2, B. Afanasyev1, A. Rumyantsev2
1Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Russia; 2Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia; 3Russian Children's Clinical Hospital, Moscow, Russia
Key words: allogeneic hematopoietic stem cell transplantation, Hurler syndrome, children, RIC, MAC
Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the treatment of choice for children with severe form of mucopolysaccharidosis type I (Hurler syndrome). The preparative regimen given to those patients is mostly myeloablative conditioning (MAC). But using of MAC is limited for patients with multisystem involvement and low Lanskoy score. Reduced intencity conditioning regimens (RIC) are associated with lower rates of severe toxicity, from another side, RIC is the risk factor for graft failure in Hurler syndrome (HS) patients.
Aim. To compare efficacy of allo-HSCT with RIC versus MAC in children with Hurler syndrome.
Materials and methods. From 2004 to 2015 unrelated allo-HSCT were performed in 31 patients with HS. Median age at the time of diagnosis was 15 months (3-24 months), at transplantation - 22 months (from 9 months to 42 months) (RIC - 28 months, MAC - 18 months). Five patients (16 %) received allo-HSCT from HLA-matched related, 26 (84 %) - from matched (n=23) or partially matched (9/10) (n=3) unrelated donors. The donor sources were bone marrow (BM) (n = 19, 61.3 %), peripheral blood stem cells (PBSC) (n = 10, 32.2 %) or cord blood (n = 2, 6.5 %). The myeloablative (Busulfan or Treosulfan-based) and reduced-intensity (consisted of Fludarabine, Melphalan and ATG) conditioning
regimens were used in 23 (74 %) and 8 (26 %) patients respectively.
Cyclosporine A or Tacrolimus plus short course of methotrexate or MMF were used for GVHD prophylaxis. In 3 cases immunomagnetic CD3/CD19+-depletion of PBSC (by CliniMACS) was used additionally.
Results. Median follow up was 50 months (range 7- 140 months). 27 patients are alive. Overall survival - 69.5 ± 0,16 % (MAC - 72.75 %, RIC - 75 %, P = 0.24). The median time to neutrophil recovery > 0,5 x 109/L was 20 days (11-29). All patients were engrafted with achievement of full donor chimerism and normal alpha-L-iduronidase activity in leucocytes on D+30. In 7 cases (2 (25 %) after RIC and 5 (22 %) after MAC, P = n.s.) decreasing of donor chimerism was observed. Graft rejection was observed in 5 (16 %) patients (MAC - 4 (17 %), RIC - 1 (12.5 %), P = n.s.). During RIC alloHSCT none patients developed severe toxicity (grade III-IV according to NCI CTC ver. 3.0 criteria). Seven (30 %) patients after MAC had mucositis grade III. Results of hepatic tests did not differ significantly between the two groups. Seventeen (74 %) patients in the MAC group had grades II-III skin toxicity compared with none in the RIC group (P=0.002). There were no statistically significant differences in acute and chronic GVHD rates.
¡][¡ The main reason of death in the MAC group was lung infection. One patient in the RIC group died from acute GVHD, 1 patient died due to TRALI-syndrome.
Conclusion. Our data demonstrate that RIC regimens resulted in comparable overall survival rates with MAC regimens in Hurler syndrome patients. MAC was associated with higher risk of severe mucositis and skin toxicity. There was no statistically significant difference in rejection rate between patients conditioned with MAC and those conditioned with RIC.
OF PEDIATRIC HEMATOLOGY and ONCOLOGY
ABSTRACT NO.: OP-373
Single-center study of outcome of hematopoietic stem cell transplantations:
10/10 versus 9/10
N. Sidorova1, K. Kirgizov1, D. Balashov2, P. Trachtman2, M. Persiantceva2, E. Pristanskova1, V. Konstantinova1, O. Blagonravova1, M. Maschan2, E. Skorobogatova1, A. Maschan2
1Russian Children's Clinical Hospital, Moscow, Russia; 2Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: HSCT, ALL, AML, MUD, MMUD, a.GVHD, Tacro/Mtx scheme
Introduction. MUD HSCT is routine method now. Importance of HSCT from 9/10 and 10/10 MUD is discussed.
Aim. To compare the efficacy of allo-HSCT from MUD (10/10) and MMUD (9/10) for children with hematological malignancies.
Materials and methods. 97 HSCT from 9/10 and 10/10 MUD performed during the period 2003-2014. Diagnosis: AML - 68 % (n = 66), ALL - 32 % (n = 31). Gender distribution: male - 71 % (n = 69), female - 29 % (n = 28). Age median - 8.3 y.o. (1-17 y.o.). Stem cell source: BM - 80 % (n = 77), PBSC - 20 % (n = 20). 77 pts. (79 %) received 10/10 MUD HSCT and 20 pts. (21 %) - 9/10 MUD HSCT. Conditioning regimen contained different agents due to protocol and type of disease. The type of a.GvHD prevention therapy carried cyclosporin A (CsA)/methotrexate (Mtx) until 2007, tacrolimus (Tacro)/CellCept (MMF) from 2007 to 2011 and from 2012 used a combination Takro/Mtx.
Results. Overall incidence of a.GvHD (I—IV st.) in 10/10 group was 69 % (n = 53) and in 9/10 - 80 % (n = 16), a. GvHD (III-IV st.) incidence - 16 % (n = 12) and 30 % (n = 6) accordingly. We revealed that type of a.GvHD prevention therapy can significantly improve outcome: Tacro/MTX prevention better in comparison with other types (Tacro/MMF and others). In both groups during the Tacro/MTX scheme have been no cases of a. GvHD (III-IV st.). Infection's episodes weren't significantly different in 9/10 and 10/10 groups. In 10/10 group at median follow up of 12.2 years, the estimated probability of OS was 56 % and in 9/10 group OS was 30 %, median follow-up - 11.8 years.
Conclusion. Our results suggest that 10/10 transplants have better outcome and lower incidence of severe a. GvHD. Tacro/MTX scheme can decrease a.GvHD (I-IV st.) episodes in both groups. Our experience showed that 9/10 results improved in past several years. Now 9/10 transplants is good option in case of absence 10/10 donor.
ABSTRACT NO.: OP-375
The efficiency of the conditioning regimen at hematopoietic stem cells transplantation from HLA-matched (10/10) and mismatched (9/10) unrelated donors for children
with hematological malignancies
N. Sidorova1, K. Kirgizov1, D. Balashov2, P. Trachtman2, M. Persiantceva2, E. Pristanskova1, V. Konstantinova1, O. Blagonravova1, M. Maschan2, E. Skorobogatova1, A. Maschan2
1Russian Children's Clinical Hospital, Moscow, Russia; 2Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: HSCT, ALL, AML, a. GVHD, MUD, MMUD, MAC-Treo
Introduction. Hematopoietic stem cell transplantation (HSCT) from unrelated donors is an accepted treatment of patients with oncohematological diseases. Probability of identification of HLA-matched donor is only 70-75 %.
Aim. To evaluate the efficiency of the conditioning regimes used in HSCT from HLA-matched (10/10) and mismatched (9/10) unrelated donors for children with hematological malignancies method of retrospective analysis.
Materials and methods. The study included 97 HSCT from unrelated donors performed in the period 2003-2014. 71 % (n = 69) were male, while 31 % (n = 28) were females. The age of patients 1-17 years (median 8.3 years). Nosological structure: AML - 68 % (n = 66), ALL is a 32 % (n = 31). The source of stem cells: BM - 79 % (n = 77), PSCC - 21 % (n = 20). 79 % (n = 77) patients, HSCT was performed from HLA-matched (10/10) unrelated donor and 21 % (n = 20) from mismatched (9/10). At the time of HSCT was 65 % (n = 63) patients were in complete remission and in 35 % cases (n = 34) noncomplete remission. Conditioning regimes: MAC-TBI 2 % (n = 2), MAC-Treo 17 % (n = 16), MAC-Treo-Mel 32 % (n = 31), MAC Bu 5 % (n = 5), MAC Bu-Mel 41 % (n = 40) and RIC 3 % (n = 3). GVHD prophylaxis was performed with cyclosporine A(CsA)/methotrexate(Mtx) until 2007, tacrolimus (tacro)/CellCept (MMF) from 2007 to 2011, and since 2012 has used a combination of tacro/Mtx.
Results. The best score by level of overall survival was detected in patients receiving HSCT from a 10/10 donor, after conditioning the MAC-Treo was 85 % (n = 11). Overall survival of patients after HSCT 10/10 and MAC-Bu-Mel 54 % (n = 15), MAC-Treo-Mel 50 % (n = 14), RIC 33 % (n = 1), MAC-Bu 25 % (n = 1) and MAC-TBI 0 %. When performing HSC transplantation from mismatched unrelated donors 9/10 overall survival was: MAC-Treo 33 % (n = 1), MAC-Bu-mel 33 % (n = 4), MAC-Treo-mel 33 % (n = 1), RIC 33 % (n = 1), MAC-Bu 0 %, MAC-TBI 0 %. The level of the two-years relapse free survival of patients after HSCT from 10/10 and 9/10 donor was 56 % (n = 43) and 30 % (n = 6), respectively. Conclusion. By performing HSCT from HLA-matched (10/10) and mismatched (9/10) unrelated donors the choice of conditioning regimen influences at the HSCT outcome. The use of MAC-Treo associated with better OS and two-years RFS, and is the best option in HSCT from an unrelated donors in children with hematological malignancies.
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