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ABSTRACT NO.: PP-099
The efficacy of cyclosporin in the treatment of infant case with subcutaneous panniculitis-like T-cell lymphoma (SPTCL)
Key words: subcutaneous panniculitis-like T-cell lymphoma, cyclosporin, immunosuppressive therapy, combination chemotherapy
Introduction. SPTCL is an extremely rare type of cutaneous lymphoma in infants. We herein present a case of pediatric SPTCL that showed a good response to immunosuppressive therapy with cyclosporine (CyA).
Aim. This case is special for two reasons: first, it is the youngest reported case of SPTCL in the literature; and second, we obtained a desirable treatment response with CyA in spite of the patient's poor response to combination chemotherapy.
Materials and methods. Case. A 1-month-old male presented with multiple erythematous subcutaneous nodules on his earlobe, cheek, hips, and upper and lower extremities. He was diagnosed with SPTCL based on the characteristic pathological findings in a skin biopsy specimen. Because he had no clinical findings except broad skin involvements, we initially managed him with prednisolone monotherapy. Although we observed a rapid improvement of his skin disease, a few nodules persisted and gradually spread as the prednisolone dose was tapered. We then administered combination chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin and prednisolone (CHOP). During the administration of prednisolone his skin nodules improved, but it worsened as soon as the prednisolone treatment was terminated. We concluded that the combination chemotherapy was not effective for treating his disease.
Results. Based on the fact that prednisolone was partially effective in treating the patient's disease, we considered that immunosuppressive agents such as cyclosporine and tacrolimus might affect his skin disease. He was therefore treated with CyA (6 mg/kg/day, orally). All of his subcutaneous nodules disappeared and did not reemerge during drug tapering.
Conclusion. The standard treatment for SPTCL is multi-agent combination chemotherapy. It is unclear why combination chemotherapy was not effective in this case. It is possible that the dormancy of the SPTCL cells may be related. Therefore, immunosuppressive treatments with CyA for SPTCL may be effective when combination chemotherapy is ineffective.
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Michihiro Yano, Miwa Hebiguchi, Koya Kodama, Tsutomu Takahashi
Akita University Hospital
ABSTRACT NO.: P-103
Modern aspects of differential diagnosis and treatment of large B-cell lymphomas with mediastinal involvement in children and adolescents
A.S. Levashov, A.M. Kovrigina, A.M. Stroganova, T.T. Valiev, A.V. Popa
N.N. Blokhin Russian Cancer Research Center, Moscow, Russia
Key words: large B-cell lymphomas, mediastinal involvement, children, differential diagnosis, molecular-biological markers
Introduction. At the present time results of some pediatric protocols (FAB/LMB96 with and without rituximab, B-NHL-BFM90/95, B-NHL-2004m) were published but prognostic and diagnostic significance of markers, such as: C-MYC, STAT3, pSTAT3tyr705, TRAF1, TNFAIP2 expression, C-MYC gene rearrangement and amplification in childhood large B-cell lymphomas with mediastinal involvement (diffuse large B-cell lymphoma - DLBCL, primary mediastinal (thymic) large B-cell lymphoma - PMLBCL) is unknown. Aim. The aim of this study was to determine distinctive molecular-biological features of childhood large B-cell lymphomas with mediastinal involvement, to estimate the significance of these markers for overall survival (OS), event-free survival (EFS) and progression-free survival (PFS).
Materials and methods. From 1994 to 2015 twenty two pediatric patients with large B-cell lymphomas with mediastinal involvement were included in trials IDM-NHL-BFM90, B-NHL-BFM 95 ± rituximab (10 with DLBCL, 12 with PMLBCL). Male/female ratio was 1/2. Median age - 12.2 ± 0.6 years (range from 5 till 18). Minimal age of patients with DLBCL was 5 years, for patients with PMLBCL - 10 years. Stage III-IV, R3-R4 risk groups were revealed in all patients (100 %). GCB/non-GCB DLBCL subtypes were assessed by Hans and Visco-Young immunohistochemical algorithms. Cutoff values of 40 % for MYC, 70 % for BCL2, 20 % for STAT3, 50 % for pSTAT3tyr705, TRAF1, TNFAIP2 were established. MYC gene rearrangement and amplification were assessed by FISH using locus-specific MYC (8q24) tricolor break apart probe and MYC (8q24) SE8 control probe. Results. Molecular portrait of childhood primary mediastinal (thymic) large B-cell lymphoma was characterized by: CD20 expression in all patients, high frequency of CD23, CD30, C-MYC, PAX5, TRAF1, TNFAIP2 expression, absence of CD10, p-STAT3tyr705 expression, low frequency of IgM expression, absence of C-MYC gene rearrangement and/or amplification despite the level of C-MYC expression more 70 %, high activity of JAK2-JMJD2C epigenetic regulation of p-STAT3tyr705-independent C-MYC expression. While molecular features of childhood diffuse large B-cell lymphoma with mediastinal involvement included: CD20 expression in all patients, non-GCB variant, high frequency of C-MYC expression, C-MYC gene rearrangement, absence of CD23, TRAF1, TNFAIP2 expression, low frequency of CD30 expression.
Using protocol B-NHL-BFM-95 plus rituximab we have achieved high level of progression-free survival in patients with large B-cell lymphomas with mediastinal involvement (100 %, a median follow-up was 50 ± 16.7 months; only for patients who completed whole program therapy).The influence of investigated markers (CD23, CD30, C-MYC, STAT3, p-STAT3tyr705) on OS, EFS and PFS was not observed.
Conclusion. Number of patients in this study is not sufficient for estimation of prognostic significance of these markers but high-intensive B-NHL-BFM-95 + rituximab chemotherapy showed good therapeutic effect in our patients. This study will be continued.
ABSTRACT NO.: PP-106
Cytogenetic adverse prognostic factors in childhood Burkitt lymphoma
A.S. Fedorova, E.V. Volochnik, R.I. Yutskevich, O.V. Aleinikova
National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus
Key words: Burkitt lymphoma, cytogenetic, prognosis
Introduction. Inspite of good treatment results of children with Burkitt lymphoma (BL) and low recurrence rate, prognosis for patients (pts) with disease failure is dismal. Therefore search for relapse predictors remains actual. There are few reports concerning adverse prognostic value of such chromosomal abnormalities as del13q32, gain 7q, dup(1)(q12q32) in limited cohorts of pts.
Aim. We aimed to analyze BL cytogenetic findings and their prognostic significance.
Materials and methods. A total of 56 BL pts from 2 to 23 years old (median age, 8) diagnosed in our hospital in 1998-2015 were studied. M/F ratio was 5.2/1. Three pts had stage I tumor, 6 - II, 14 - III, 9 - IV, 24 - leukemia. Pts were treated according to consecutive BFM-based regimen (modified NHL-BFM-90/95, B-NHL-M-2004/2010 (Russia)). Probability of 5-y EFS was 0.75 for all studied pts. Chromosomal analysis was performed using conventional cytogenetic analysis (G-banding) in 53 newly diagnosed and in 3 relapsed pts with BL. Results. Detection of dup(13)(q14q32) was associated with primary abdominal site (in 5 of 6 cases) and high relapse rate of 66.7 % (pf 10 and 2 years (stage IIR in 1pt; stage IV (BM + CNS) in 1 pt, who received high dose chemotherapy and autologous heamotopoietic stem cell transplantation after the 5th course of conventional chemotherapy). Monosomy of chromosome 17 was detected in 4 pts, all of them died of tumor progression (P = 0.00001).
Conclusion. Karyotypes of BL cells showed a high degree of diversity and complexity. Detection of dup(13)(q14q32) or monosomy 17 are associated with unfavorable prognosis.
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ABSTRACT NO.: P-145
Hodgkin lymphoma in young adults
S.A. Kulyova, A.P. Karitsky, S.V. Ivanova
N.N. Petrov Research Institute of Oncology, Saint Petersburg, Russia
Key words: young adults, Hodgkin's lymphoma, survival rate
Introduction. Young adults represent a unique cohort of the population with high level of malignant tumors incidence. Hodgkin's lymphoma (HL) makes about 12 % of all tumors at 19-29-year-old patients. Young adults isn't rather investigated since treatment it is carried out in various options according to different programs (pediatric and adult), and the remote consequences of therapy in such patients aren't studied. Aim. The purpose of our investigation was to assess of therapy for Hodgkin's lymphoma in young adults.
Materials and methods. From January 1995, to July 2011, 87 patients aged from 19 to 29 years old (median 24 ± 4 years old) with biopsy-proven HL were treated at the N.N. Petrov Research Institute of Oncology. There were 34 (39.1 %) men and 53 (60.9 %) women (the male-to-female ratio was 2.1 : 1). B symptoms occurred in 47 patients (54 %). There were 47 patients (54 %) with clinical stage I-II and 40 (46 %) - with stage IV. Extranodal involves is revealed in 37 patients (42.5 %). The distribution of the HL according to the histological classification was as follows: 76 patients (87.4 %) had nodular sclerosis, 5 (5.7 %) - mixed cellularity, 2 (2.3 %) - lymphoid predominant type and 4 patients (4.6 %) were unclassified due to unsufficient quality of the specimens obtained. All patients were given 2-11 cycles of primary chemotherapy (median 4 cycles) with ABVD (48 patients, or 55.2 %), BEACOPP (36, or 41.4 %), MOPP (2, or 2.3 %) and COPP (one patient). Chemotherapy regimen was followed by extend- or involved- or subtotal radiation with doses from 20 to 51 Gy in 57 patients (65.5 %).
Results. All patients were assessed for the treatment results. With a median of 31 months of follow-up (range, from 3 to 156 months) the freedom from treatment failure of 3 years after diagnosis was 47.4 % (SE - standard error - 7.8 %), event-free survival was 70.5 % (SE 7.2 %), and overall survival was 82.7 % (SE 5.2 %). Of the 72 patients who received the therapy and achieved a complete remission, 19 (21.8 %) relapsed at a median time of 31 months from initial diagnosis (range, 7 to 80 months). Conclusion. Low survival in young adults with HL confirm need of change of combined modality therapy role with transition on using principle of risk-adapted treatment that will allow to achieve good results, and to decrease side effects of follow-up.
ABSTRACT NO.: P-146
The influence of "bulky" disease on survival in patients with Hodgkin lymphoma
S.A. Kulyova, A.P. Karitsky, S.V. Ivanova
N.N. Petrov Research Institute of Oncology, Saint Petersburg, Russia
Key words: young adults, Hodgkin lymphoma, "bulky" disease
Introduction. About 70 % of patients with the Hodgkin lymphoma (HL) may be cured. The analysis of various predictive factors is applied to identification of the remained patients who need intensive therapy. "Bulky" disease is the most important parameter which directly has impact on survival of patients with malignant tumors. Aim. The aim of the study was the assessment of tumor burden's components (a mediastinum/thoracic ratio - MTR, peripheral bulky disease, and number of involved lymph nodes) in young adults with Hodgkin lymphoma and the analysis of their predictive value.
Materials and methods. Data on 87 patients aged from 19 till 29 years (median 24 ± 4 years) are submitted. The male-to-female ratio was 2.1 : 1. B symptoms occurred in 47 patients (54 %). There were 47 patients (54 %) with clinical stage I-II and 40 (46 %) - with stage IV. Extranodal involves is revealed in 37 patients (42.5 %). The distribution of the HL according to the histological classification was as follows: 76 patients (87.4 %) had nodular sclerosis, 5 (5.7 %) - mixed cellularity, 2 (2.3 %) - lymphoid predominant type and 4 patients (4.6 %) were unclassified due to unsufficient quality of the specimens obtained.
Results. The optimum cut-off level according ROC method for MTR has been established at 0.33, for peripheral bulky disease has been established at 46 mm, and for number of involved lymph nodes has been established at 5. Use of the correlation and regression analysis allocated the best linear regression model for MTR with the maximum determination coefficient and the minimum residual dispersion (P = -0.928971 + 4.008252x). There were statistically significant the equation by Fischer's criterion and determination coefficient (Ffact(46.74) > Ftheor(4.17)). Linear and nonlinear regression models for "a peripheral lymphadenopathy" and "number of involved zones" didn't show significant influence on the outcome (P = 0.9237 and P = 0.3385, respectively). MTR significant influenced the late results. The disease-free survival in patient's group with MTR less than 0.33 was 100 %, ^ in group with MTR more than 0.34 was 41 % (log-rank test 0.04649).
^ Conclusion. The study proved that mediastinum/thoracic ratio is the significant prognostic factor. Such factors as "a peripheral lymphadenopathy" and "number of involved zones"
q had smaller predictive value. These components are indicators of "bulky" disease and demand further studying.
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ABSTRACT NO.: P-147
Pair linear dependence of prognostic factors with a tumor volume in young adults
with Hodgkin's lymphoma
S.A. Kulyova, A.P. Karitsky, S.V. Ivanova
N.N. Petrov Research Institute of Oncology, Saint Petersburg, Russia
Key words: Hodgkin's lymphoma, tumor volume, young adult
Introduction. Hodgkin's lymphoma in young adult is an aggressive disease with poorer prognosis than in childhood.
Aim. The aim of study was creation of the pair linear dependence equations of prognostic factors with factor «the tumor volume».
Materials and methods. 87 patients aged from 19 to 29 years old (median 24 ± 4 years old) with Hodgkin's lymphoma were treated at the N.N. Petrov Research Institute of Oncology in 1995-2011. The male-to-female ratio was 2.1 : 1: there were 34 (39.1 %) men and 53 (60.9 %) women. Forty-seven (54 %) had B symptoms. There were 47 patients (54 %) with clinical stage I-II and 40 (46 %) - with stage IV. Thirty-seven patients (42.5 %) had E-stage. The distribution of the HL according to the histological classification was as follows: 76 patients (87.4 %) had nodular sclerosis, 5 (5.7 %) - mixed cellularity, 2 (2.3 %) - lymphoid predominant type and 4 patients (4.6 %) were unclassified. All patients were given 2-11 cycles of primary chemotherapy (median 4 cycles) with ABVD (48 patients, or 55.2 %), BEACOPP (36, or 41.4 %), MOPP (2, or 2.3 %) and COPP (one patient). Chemotherapy regimen was followed by extend- or involved- or subtotal radiation with doses from 20 to 51 Gy in 57 patients (65.5 %).
Results. The pair correlation method was carried out for an assessment of narrowness, a vector and analytical expression of parameters communication with a tumor volume. Haemoglobin (y[haemoglobin] = - 1.407407 + 0.259259x[volume], r = 0.018730), fibrinogen (y[fibrinogen] = 1.250000 + 0.350000x[volume], r = 0.028944), LDG (y[LDG] = 0.85185 + 0.148148x[volume], r = 0.020156) and no effective therapy (y["-"effect] = 0.370370 + 0.387205x[volume], r = 0.000332) and B-symptoms (y[B-symptoms] = 1.413043 + 0.232118x[volume], r = 0.046422) had significant communication with tumor volume.
Conclusion. Allocation of pair correlation and creation of correlation model allows to consider these factors as possessing a multicollinearity, they can be intercorrelated and excluded from the final multifactor analysis.
ABSTRACT NO.: P-157
Positron emission tomography in diagnosis of malignant lymphomas in children
I.I. Badrtdinova1, R.R. Bayramgulov1, O.N. Lipatov2, D.A. Sinilo1
Republican Children's Clinical Hospital, Ufa, Republic of Bashkortostan; 2Bashkirian State Medical University, Ufa, Republic of Bashkortostan
Key words: malignant lymphomas, children, positron emission tomography/computed tomography with 18F-fluorodeoxyglucose, diagnosis
Introduction. Malignant lymphomas in children are a heterogenous group of diseases in the context of which treatment and prognosis are determined by adequate staging and follow-up/observation. A standard imaging procedure is computed tomography (CT). Positron emission CT with 18F-fluorodeoxyglucose (PET/CT with 118F-FDG) can play a promising role in the diagnosis of malignant lymphomas in children.
Aim. To investigate the role of PET/CT with 18F-FDG for staging, treatment planning and response assessment in children with malignant lymphomas. Materials and methods. During the period 2014-2015 in the Republic of Bashkortostan, 34 PET/CT with 18F-FDG imaging exams were performed in 20 children (girls - 6, boys - 14; all children aged 0-18 years old) with histologic diagnosis "malignant lymphoma" (Hodgkin lymphoma (n = 12), Burkitt lymphoma (n = 3), anaplastic large cell lymphoma (n = 2), T-lymphoblastic lymphoma (n = 3), B-lymphoblastic lymphoma (n = 1)). Investigations were performed both for disease staging, intermediate assessment («response-controlled» treatment) and for the control of treatment. 18F-FDG PET/CT findings were compared with the results of CT with intravenous contrast (IV contrast). Tumour process extent was evaluated based on the analysis of 18F-FDG PET/CT findings, CT scans with IV contrast only as well as findings of 18F-FDG PET/CT and CT with IV contrast performed simultaneously. Inclusion criteria for the investigation were: the availability of protocols and medical images (CT with IV contrast, PET/CT with 18F-FDG). The investigation was performed only for FDG-sensitive lymphomas. The period of the investigation was limited to the period of follow-up after the performed investigations (median follow-up duration - 12 months). Results. PET/CT with 18F-FDG is a more effective method for detection of lymphatic tissue involvement (sensitivity - 93 %, specificity - 100 %) in comparison with CT with IV contrast (sensitivity - 88 %, specificity - 86 %). In case of extranodal involvement, this method also has the advantage (sensitivity - 88 %, specificity - 100 %) over CT with IV contrast (sensitivity - 50 %, specificity - 90 %). The analysis of patients who underwent simultaneously performed PET/CT with 18F-FDG and CT with IV contrast showed the best result, proper <
treatment tactics was accepted in 100 % of cases, and this rate was higher than in case of CT with IV contrast (35 %).
Conclusion. PET/CT with 18F-FDG should be applied for staging of FDG-avid lymphomas, detection of residual foci in lymph nodes and extranodal involvement during the treatment
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as well as when disease recurrence is suspected. CT with IV contrast should be applied in the staging of FDG-negative lymphomas. Simultaneous performance of 18F-FDG PET/CT ^
and CT imaging with IV contrast is considered reasonable for optimal anatomical assessment of involved areas, adequate staging and control of treatment process. $
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ABSTRACT NO.: P-199
Intensive therapy children with advansed stage Hodgkin's lymphoma
E.S. Belyaeva
Pediatric Oncology and Hematology Research Institute of N.N. Blokhin Russian Cancer Research Centre, Moscow, Russia Key words: Hodkin's lymphoma, BEACOPP, advansed stage
Introduction. The treatment results of children with local stage of Hodgkin's lymphoma (LH) are not bed, but the treatment results patients with advanced stage of LH aren't satisfied. Aim. We decided to study efficacy and toxicity of chemo (escBEACOPP).
Materials and methods. From 2003 to 2015 103 pts (female 53, male 50) with advanced stage LH were enrolled in this study. The median age was 12.5 y. (3-18). Primary staging was: stage II - 34 pts (33 %) with bulk disease (mediastinal mass greater than 1/3 of the mediastinal thoracic diameter and/or nodal aggregate greater than 10 cm), stage III - 23 pts (22.3 %), stage IV - 46 pts (44.7 %). Therapy induction consisted on 4 courses of escBEACOPP (Cyclophosphamide - 1200 mg/m2/d, days 1, Etoposide - 200 mg/m2/d, days 1-3, Doxorubicin 35 mg/m2/d, on day 1, Bleomycin 10 U/m2/d, days 8, Vincristine 1,5 mg/m2/d, days 8, Procarbasine 100 mg/m2/d, days 1-7, Prednizone 20 mg/m2/d, days 1-14). Consolidation was different for females and males and also depended on response to 4 courses of indaction. Females with a good response to therapy (CR, PR1 - 70 % reduction in disease) received 4 courses COPP/ABV (Cyclophosphamide - 600 mg/m2/d, days 1, Doxorubicin 35 mg/m2/d, on day 8, Bleomycin 10 U/m2/d, days 8, Vincristine 1,5 mg/m2/d, days 1, Vinblastine 6 mg/m2/d, days 8, Procarbasine 100 mg/m2/d, days 1-7, Prednizone 20 mg/m2/d, days 1-14) without RT. Male with CR or PR1 received 2 courses ABVB (Doxorubicin 25 mg/m2/d, on days 1, 15, Vinblastine 6 mg/m2/d, days 1, 15, Bleomycin 10 U/m2/d, days 1, 15, Dacarbazine 375 mg/m2/d, days 1, 15) with involved field RT 20 Gy. Results. Complete response after 4 courses got 32 pts (31.1 %), PR1 - 55 pts (53.4 %), PR2 - 15 pts (14.6 %), SD - 1 pts. Thirty-nine females haven't got RT (3 - developed relapse with a still but in second CR).
Median follow-up is 145.0 ± 2.4 mo, RFS = 91.5 ± 2.9 %; EFS = 89.6 ± 3.1 %; OS = 97.0 ± 1.7 %.
In spite of severe hematological toxicities - grade IV 45.6 % just two patients had fatal infection and one grade III mucositis. There were no any non- hematological toxicity. Conclusion. We suggest that escBEACOPP regimen is tolerable and shows good treatment results in patients with advanced stages HL.
ABSTRACT NO.: P-219
Burkitt's lymphoma in children: Is a second CVP effective in critically ill children?
Emad A.H. Moussa1, Asmaa M. Hamoda2, Samah F. Semary3, Marwa Romeih4, Randa Amin5, Omneya Hassanin6
1Dept Clinical Oncology-Menofiya University, Consultant PHO at CCHE; 2DeptPediatric Hematology/Oncology-NCI - Cairo University, Consultant PHO at CCHE; 3Pediatric Oncology-Faculty of Medicine-Beni Suef University, and Consultant PHO at CCHE; 4Radiodiagnosis -NCI - Cairo University, Consultant Radiodiagnosis at CCHE; 5Pathology-Faculty of Medicine-Assiut University, and Consultant pathology at CCHE; 6CRA at CCHE
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Key words: Burkitt's lymphoma, pediatrics, induction chemotherapy
Introduction. Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents. A progress has been achieved, with survival rates exceeding 80 %. Patients with advanced-stage disease are at significant risk of roughly 3 % to die from treatment related complications, especially during the first phase of therapy. Protecting those patients from the acute and/or chronic toxicity of antineoplastic therapy has become a major concern of oncology centers around the world. Aim is to analyze the outcome of those critically ill patients who could not continue to have Induction phase and were given a second CVP, and to measure the delay period before which those patients started their first COPADM course.
Materials and methods. Children with Burkitt's lymphoma, less than 18 years and assigned to LMB96 protocol at CCHE. Their data between 7/2007 till end of 10/2015 were retrospectively collected. They all had a second CVP after a pre-induction phase due to: 1-Renal failure, or creatinine clearance 10 folds. An initial full laboratory workup, whole body CT scan, PET scan, bilateral bone marrow aspirate and biopsies and a CSF analysis were all done for all cases as well as an initial baseline cardiogram. A biopsy, will is obtained from all patients.
Results. 45 patients received 2nd CVP 29 males and 16 females The site of primary disease was abdominal in 34 patients, pelvic in 5, iliac bone in one, ovarian in one, lumbar mass in one, bilateral renal mass in one, paraspinal in one, and maxillary sinus in one. Nineteen patients were stage IV, while 26 patients were stage III. Twenty five patients were group C (55.5 %), and 20 were group B (44.5 %). After the 1st cycle of CVP, 8 had stationary disease, 34 had Regressive disease while 3 showed progressive disease. A second CVP was given due to renal impairment in 3 patients, 3rd space fluid accumulation in 17 patients, 6 patients had convulsions, one patient had encephalitis, while 4 patients had very poor general condition. After a follow up period ranged from 17 days to 8.083 years, 29 were alive (64.5 %), while 16 patients (35.5 %) died (7 died immediately post 2nd CVP). Five patients died from disease progression, 10 patients died from septicemia, one from multisystem organ failure. The period until patients had their Induction phase (COPADM-1) ranged from 6-45 days. Conclusion. In mature B cell lymphoma of children and adolescence a second CVP is tolerated in ill patients but with a high price (35.5 % death) An alternative approach for those patient who cannot tolerate induction should be searched for.
ABSTRACT NO.: PP-234
Evaluation of morbidity, mortality and survival in children and young adolescents with malignant lymphomas in Arkhangelsk region in 2003-2014
N.A. Grigoreva
Arkhangelsk Regional Children's Clinical Hospital named after P.G. Vyzhletsov, Russia Key words: malignant lymphomas, incidence, mortality, children, non-Hodgkin's lymphomas, Hodgkin's lymphomas, 5-year survival
Introduction. The incidence of malignant lymphomas (ML) still stays one of the first places, gives way only for leukemias and brain tumors. According to US authors annually about 55 % of all ML are non-Hodgkin's lymphomas (NHL). 5-year survival rate in Hodgkin's lymphoma (HL) is nearly 95 % when this disease was detected early, and it is nearly 90 % after late diagnosis. 5-year event-free survival in NHL is 80 %; this index is up to 90 % when NHL was detected early and in localized forms of NHL. Analysis of the incidence and survival of the patients with ML is highly relevant in modern society from the standpoint of pharmacoeconomics, demography, improving the quality of life of the patients. Aim. To evaluate the incidence, mortality and 5-year survival of patients with ML in Arkhangelsk region in 2003-2014.
Materials and methods. The analysis was performed on the database of medical records of Arkhangelsk Children's Hospital, of Cancer Registry of Arkhangelsk Regional Clinical Oncology Center.
Results. During 12-years period total were 52 patients with ML. From them 26 had NHL (50 %) and 26 had LH (50 %). Age of primary diagnosis of NHL was from 2.5 to 17 years old (a median is 11.5 years old), age of primary diagnosis of LH was from 4 to 17 years old (a median was 15 years). Among patients with LH there were 4 children with I (15.4 %), 13 - with II (50 %), 4 - with III stage (15.4 %) and 5 - with IV stage (19.2 %). Among patients with NHL there were 2 children with II stage (7.7 %), 9 - with III stage (34.6 %) and 15 patients with IV stage (57.7 %). Primary incidence of all ML was maximal in 2003 (3.56 per 100 000) and minimal in 2008 (0,82 per 100 000), annual incidence of malignant lymphomas was 1.79 ± 0.21 per 100 000. Primary incidence of NHL was 1.8 per 100 000 in 2013 (maximal) and 0.0 in 2011; primary incidence of LH was 2.1 per 100 000 in 2009 (maximal) and 0.0 in 2004 and 2013. Maximal level of mortality in children with ML occurred in 2003 and amounted to 2.22 per 100 000 children; the lowest level of mortality in children with ML was in 2007 (0.40 per 100 000). In 2006, 2009-2014 we did not registered deaths among children with ML. 5-year survival (by Kaplan-Meyer) according nosology was: among patients with NHL 68.7 %; among patients with LH 91.8 %.
Conclusion. In the structure of ML in 2003-2014 there were NHL and LH 50 % of both. The average annual incidence of malignant lymphomas was 1.79 ± 0.21 per 100 000, this is slightly higher than European and US data, but comparable with Russian data. The median of age for NHL was 11 years, for LH it was 15 years, which is very typical for these kinds of diseases. We have found that 50 % of LH were detected in the II stage of disease. Among NHL the majority (92.3 %) of cases manifested in the III and the IV stages, and 5-year survival in LH are comparable to those in developed countries and Russian Federation. However, survival in NHL was lower (68.7 %). This was probably due to these patients were admitted to oncology departments with advanced stages of the disease, often they were in terminal condition, sometimes they were admitted after non-correct surgical interventions or too late. But in recent years there was detected decreasing of mortality in patients with malignant lymphomas, which can indirectly indicate positive experiences of a program of a therapy of malignant lymphomas and the appearance of cancer alertness among pediatricians and other related specialists.
ABSTRACT NO.: P-242
Use of blinatumomab for treatment of early bone marrow relapse of B-cell lymphoblastic lymphoma
D.A. Evstratov1, N.V. Myakova1, O.P. Khlebnikova2
1Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia;
2Children's Regional Clinical Hospital № 1, Yekaterinburg, Russia
Key words: lymphoblastic lymphoma, relapse, blinatumomab oo
Introduction. Blinatumomab belongs to a class of recombinant bi-specific T-cell engagers (BiTEs). It is single polypeptide chain, containing binding sequence for the pan-B-cell ^
antigene CD19 on the one hand and for CD3 £-chain of T-cell receptor on the other. BiTEs were developed for directing effector T cells to target cells with the activation of cytotoxic q
T-lymphocytes. Blinatumomab targets CD19 that is expressed on acute lymphoblastic leukaemia (ALL) cells and on lymphoblastic lymphoma cells. Its action results in T cell-mediated ^
killing of blast cells. To date, numerous studies of blinatumomab for the treatment of refractory ALL, including in children, were published. ^
Aim. We present a case of blinatumomab use in a child with relapsed precursor B-cell lymphoblastic lymphoma. ^
Materials and methods. Our patient is an 11-year-old boy. The diagnosis "B-cell lymphoblastic lymphoma" was established in September 2012 based on the biopsy samples of solitary soft tissue neoplasm located in the parietal region. No treatment was performed. Enlargement of lymph nodes occurred in December 2012. In March 2012 the diagnosis "Stage II B-cell lymphoblastic lymphoma with the involvement of cervical lymph nodes"was made and treatment according to the Euro-LB 2002 protocol was initiated. Three months after the end of supportive therapy (July 2015) the child started to experience intensive pain in the lumbar region, leukocytosis in blood of 20,000/mcl, blast cells - 1 %. Myelogram showed total infiltration by malignant blast cells with the phenotype CD19+/CD22cyt+/CD79a+/CD13+/CD58+/CD45+/CD56+. Cytogenetic investigation revealed trisomy 3 intact cerebrospinal fluid.
The child started to undergo treatment according to the ALL-REZ-BFM-2002 protocol in the group S3. During prophase leukocytosis continued to increase. After blocks F1-F2, a myelogram showed 2 % of blast cells, according to the findings of flow cytometry, minimal residual disease (MRD) was 1.421 %. Treatment according to the II-Ida protocol was
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carried out, after which blast cell count in myelogram was 10 %, MRD - 11 %. Thus, refractory course of disease was established. Starting from 20.11.2015 block R1 was carried out, after which a myelogram performed at points showed 3.5-3 % of blast cells, some of them had signs of anaplasia, MRD was 1.02 %. Considering high MRD in the patient with early relapse, it was decided to conduct blinatumomab treatment. On 16.12.2015 a blinatumomab course was initiated: Days 1-7 in a dose of 9 mcg/day, from Day 8 to 28 - a dose of 28 mcg/day continuous infusion. One hour before the infusion and prior to up-titration, dexamethasone in a dose of 20 mg was administered. On Day 2 of therapy a fever that was scarcely lowered by paracetamol, it was lowered only on the following day. No other toxicity was registered.
Results. Before the start of blinatumomab course, CD19+ cell count in the peripheral blood had amounted to 0.0016 x 109/l, after the therapy, CD19+ cells were not detected. The level of immunoglobulin G decreased from 8 g/l before blinatumomab treatment to 4 g/l afterwards. Myelogram performed after the end of blinatumomab course demonstrated lowered bone marrow cellularity, bone marrow of polymorphic composition, blast cell count less than 5 %. According to the results of MRD, malignant blast cell population was not found. The patient was indicated to undergo hematopoietic stem cell transplantation (HSCT).
Conclusion. The feature of this case, despite common classification category "ALL and lymphoblastic lymphoma", is that these nosological forms differ according to incidence, age, prognostic factors, treatment protocols and sensitivity to treatment. Relapses of lymphoblastic lymphoma have generally worse prognosis. Use of blinatumomab can help to overcome therapy resistance and make a patient ready for HSCT in remission.
ABSTRACT NO.: P-249
The use of Kinesio Taping according to the lymphatic correction technique in children in oncohematological practice
D.D. Shcheglova, P.M. Gorbylev
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russia
Key words: children, taping, rehabilitation, edema, ultrasound investigation, computed tomography, magnetic resonance tomography
Introduction. Lymphatic edema is one of the most frequent complications in children with oncohematological diseases. It causes the delay of recovery process and deterioration of the quality of life. In order to ensure speedy recovery and the best outcome of the main treatment it should be eliminated at the earliest stages of its manifestation. A modern approach in functional diagnosis gives reason to the development of a new complex of rehabilitation taking into account not only vascular system disorders but also the disorders of muscular and skeletal tissue that in its turn will provide a more objective monitoring assessment of the effectiveness of the current and planned rehabilitation actions. Aim. To determine diagnostically significant criteria of disorder of the pathology of the vascular system development and to develop methods of rehabilitation treatment in children with hematologic and oncological diseases by means of reducing the edema and the intensity of side-effects and complications.
Materials and methods. Ultrasound diagnosis of lymphatic malformations, magnetic resonance diagnosis (MRI) of lymphatic malformations, computed tomography (CT) with contrast enhancement of lymphatic malformations. Patients of this investigation are children undergoing rehabilitation treatment at the Treatment and Rehabilitation Scientific Centre "Russkoe Pole" of the FSBI "FRC PHOI named after Dmitry Rogachev" of the Ministry of Health of Russia.
Results. After the performed work clinical recommendations for rehabilitation treatment with due regard to the obtained data concerning lymphatic correction at all stages of treatment and children's rehabilitation will be developed. Moreover the rehabilitation treatment will be carried out during the intensive treatment. Rehabilitation, oncology and hematology, pediatrics can be potential areas of application.
Conclusion. The use of Kinesio Taping according to the lymphatic correction technique by means of reducing the edema will improve the patient's general state of health and increase physical activity, thus it will accelerate the pace of physical rehabilitation; reduce side-effects and complications after the intensive treatment; decrease the intensity of postoperative soft tissue edema as well as improve microcirculation and faster acceptance of locally advanced flaps that is especially important in children who underwent reconstructive plastic surgery on the face and neck.
ABSTRACT NO.: OP-267
A study of the demographic profile, type and treatment outcomes in paediatric non-Hodgkin's lymphoma at a tertiary care centre in Karnataka, South India
^ Arun Mundakakulathu Thomas, Appaji L, Arunakumari BS, Padma M, Avinash
O T, Madhumathi DS, Rekha V Kumar, Prasanna Kumari
^ Kidwai Memorial Institute of Oncology
S
ij Key words: lymphoma, NHL, India
Introduction. Non-Hodgkin's lymphoma (NHL) is the fifth most common cancer in children under 15 years of age and it accounts for about 7 percent of the childhood cancers in the developed world. Most Paediatric NHL's are of high grade and have an aggressive clinical behaviour. There is a lack of published literature on the frequency, distribution and survival of Paediatric and Adolescent NHL in India.
Aim. The aim of this study was to elucidate the demographic profile, histological subtype and outcome of treatment in the department of Paediatric Oncology, Kidwai Memorial Institute of Oncology (KMIO), Regional Cancer Centre for Treatment, Research and Rehabilitation, Bangalore.
Materials and methods. A systematic review was done of a total of 124 children between ages 0-15 years diagnosed with NHL at our centre from January 2009 to December 2013 in the Department of Paediatric Oncology. The information collated were the demographic profile, duration of symptoms, histological subtype of the disease, treatment and outcome. Results. Out of the 124 children with malignant NHL seen at KMIO, the median age was 7 years. The majority 86 (69.4 %) were boys and 38 (30.6 %) were girls, with a sex ratio of 2.26:1. The mean duration of symptoms was 7 weeks. The most common subtype of NHL was lymphoblastic lymphoma 49 (39.5 %) followed by Burkitt's lymphoma 44 (35.5 %), ALCL
16 (12.9 %), DLBCL 14 (11.3 %) and plasmablastic lymphoma 1 (0.8 %). The most common site was the Abdomen 43 (34.6 %), followed by Mediastinum 37 (30 %), lymph nodes and Extranodal sites like brain, liver, nasopharynx and spine. Most of the patients, 96 (77.4 %) were in St Jude Stage III at presentation. A total of 89 children (71.8 %) opted to receive treatment at our institute. The LLs were treated with ALL protocol (MCP841). Stage I and II Burkitt's lymphoma and DLBCL were treated with COMP whereas Stage III and IV Burkitt's, DLBCL and Stage I - IV ALCL were treated with MCP 842 protocol chemotherapy. The mean survival time of the children treated was 71.28 ± 2.99 months. Conclusion. NHL in children are aggressive but are treatable with excellent outcomes with good supportive care and protocol based therapy.
NO.: O -290
profile and prognostic factors in children with sporadic Burkitt's lymphoma:
An Indian experience
Smitha HV, Nita Radhakrishnan, Veronique Dinand, Anupam Sachdeva
Sir Ganga Ram Hospital, New Delhi, India
Key words: Burkitt lymphoma, survival rates
Introduction. Burkitt's lymphoma (BL) is a high-grade non-Hodgkin's lymphoma accounting for 30-50 % of all paediatric lymphomas. The event-free survival of advanced BL is 80-90 % in the developed world. There are published Indian literature which looks at disease frequency and clinical presentation of BL but none reports survival. Aim. The aim was to analyze the clinical profile, prognostic factors and survival rates in Indian children with BL.
Materials and methods. A retrospective analysis of BL was carried out from April 2009 to June 2015. Data retrieved from old records included age at diagnosis, sex, primary tumor site, tumor stage, mode of diagnosis, site of metastases, blood counts, LDH, uric acid and outcome.
Results. There were a total of 18 patients. Median age at diagnosis was 5.5 years (3-14 years) with male preponderance (78 %). Thirteen patients had stage IV and five had stage III disease. CNS involvement was observed in 8 patients. None of our patients had an early stage. Most common primary site was abdomen (16 cases, 88 %) and other two had Bell's palsy. Common misdiagnosis was hepatic abscess (2 cases), Bell's palsy (2 cases), intussuception and tuberculosis in one case each resulting in significant delay in initiation of treatment (4-12 weeks). TLS was observed in 13 patients (72 %) and eight (45 %) of them had renal failure at diagnosis. Hyperuricemia and high LDH of > 500 were seen in 66 % and 70 % cases respectively. Median follow up was 35 months. Eight patients died (7 toxic deaths and the other CNS relapse). The 5 year OS and EFS for whole cohort was 50 % and 47 % respectively. Significant difference was noted in OS and EFS between stage III (80 %, 60 %) and stage IV disease (40 %, 40 %). No significant association was noted with respect to nutritional status, uric acid, LDH, initial total leucocyte count or platelet counts and renal failure at presentation with outcome.
Conclusion. With availability of best supportive care survival rates for Pre B ALL in our center is 80 %. The same is not reflected in BL unlike developed world which could be attributed to advanced stage at diagnosis, renal failure, misdiagnosis and toxic deaths.
ABSTRACT
Clinical
ABSTRACT NO.: OP-302
Strategy of treatment children with relapse/refractory Hodgkin's lymphoma
N.S. Kulichkina, E.S. Belyaeva, G.L. Mentkevich, A.V. Popa
Pediatric Oncology and Hematology Research Institute of N.N. Blokhin Russian Cancer Research Centre, Moscow, Russia
Key words: Hodgkin's lymphoma, relapse, refractory, treatment results, autologic hematopoetic stem cells transplantation
Introduction. The modern programs for treatment children with newly diagnosed Hodgkin's lymphoma (HL) allow achieve 10-years event free survival (EFS) and disease free survival (DFS) 85-93 %, but 7-10 % of patients develop relapse and 2-5 % are initially refractory to standard chemotherapy even it was enough intensive. In Russian Federation has never been any program for treatment patients with relapse and refractory HL so children got nonprogram therapy based on OPPA, COPP, ABVD, IVA, MINE which sometimes were successful and some pts could achieve good response, but there were indefinite number of courses. And as a result, the efficacy of treatment is hampered by serious long-term adverse effects, including heart and lung disease, and secondary malignancies.
Aim. To create the program chemotherapy for children with relapse/refractory HL and to prove the effectiveness of the therapy.
Materials and methods. From July 2003 to August 2015 35 children with relapse 18 (51.4 %) and refractory - 17 (49.6 %) were enrolled to the protocol. Average 3.5-18 years
(13.5 ± 4.2), males 22 (62.9 %) and female 13 (37.1 %). From 2003 to 2007 year all the patient have got two courses of ICE (Ifosfamide, Carboplatin, Etoposide) followed by auto-HSCT. O
After getting preliminary results we made a decision to continue treating late relapsed patients by that therapy but refractory children by 4 courses ViGePP (Vinblastine, Gemcitabine, cl
Procarbasine, Prednisone) followed by auto-HSCT. Thus, therapy based on ICE got 14 (40 %) pts and ViGePP - 14 (40 %), 6 (17.1 %) children began getting ICE, but they did not S
response and therapy was shifted on ViGePP, and one (2.9 %) got two courses of ViGePP with stable disease and the therapy was shifted on two additional courses of ICE. —i
Results. Complete response (CR) was in 20 (57.1 %) patients, partial response (PR) - 14 (40 %), progressive disease (PD) - one (2.9 %). All patients five-year DFS 69.6 ± 82 %,
median follow up 95.7 ± 10.4 mo, EFS - 67.2 ± 9.4 %, median follow up 101.7 ± 9.9 mo. DFS for group of pts got the therapy based on 4 courses of ViGePP was better - 82.5 ± 11.5 %
then based on 2 courses of ICE - 56,5 ± 12.6 % and patients whose therapy was shifted on too - 57.1 ± 18.7 % (P=0,13). DFS for children with refractory and treated by ViGePP was
also better comparing with group treated by ICE: 77.1 ± 14.4 %, n = 10 and 25.0 ± 21.7, n = 4 (P = 0,047). The most important was response on therapy: DFS in patients with CR
was 88.2 ± 8.0 %, n = 20, and 43.8 ± 13.5 %, n = 15 who did not achieve CR (P=0.002). The same trend was checked in patient underwent by auto-HSCT (29 pts) and had achieved
CR before auto-HSCT then patients with PR: 84.8 ± 10 %, n = 16 and 44 ± 14.1, n = 13 (P = 0.012). Auto-HSCT was not made for 6 children - one died from disease progression,
two pts with early relapse had got a heart failure and lungs fibrosis, one with early relapse but achieved CR after the 2nd ViGePP - refused from the procedure and two had got late
relapse and CR after the 2nd ViGePP. Five children who did not get auto-HSCT but achieved CR are in complete remission and alive (median follow up 4 years).
Conclusion. Thus, children with relapse and refractory HL are curable by the program intensive chemotherapy. The most significant factors for survival were CR achievement and use
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induction treatment regime consisted on 4 courses of ViGePP. Regime based on ViGePP can be suggested as a standard induction therapy for relapse/refractory HL. Chemotherapy can be shifted on different regime if the previous one has been failed.
ABSTRACT NO.: PP-381 Venous thromboembolism in children and adolescents with non-Hodgkin's lymphoma
I. Begun, R. Tarasevich, I. Papkevich
National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus
Key words: venous thromboembolism, non-Hodgkin's lymphoma, ultrasonography
Introduction. Thrombotic complications - the actual problem of pediatric oncology. During the last 10 years was established the rising incidence of diagnosis of venous thromboembolism (VTE) in children with malignancies, which is consistent with global trends. The method of choice for the diagnosis of VTE is the Ultrasonography. This is an affordable, non-invasive and informative method of diagnosis of this pathology in pediatric cancer patients.
Aim. To analyze the frequency and semiotics of defeat of symptomatic thrombotic complications in children with NHL during treatment of the underlying disease. Materials and methods. An retrospective analysis of cases of venous thrombosis in 3733 children and adolescents with malignancies was made. All of patients received treatment in our centre from 2001 to 2014. In the protocols ultrasound and medical histories found 128 patients with first diagnosed venous trombosis aged 1-21 years (median 13 years) for both sexes. The data were processed from 234 patients with NHL too. From they were chosen who had of clinical and ultrasound symptoms of the presence of thrombotic masses in the lumen of the main veins.
Results. Venous thrombosis have been installed in 17 patients with NHL aged 4-18 years (median 15 years). From morphological variants most widespread was T-lymphoblastic lymphoma (40 %). From mediastinal localizations predominated (65 %). In two cases on prehospital the VTE was as one of the first disease manifestation. Trombotic masses were located in the subclavian and/or internal jugular veins (76 %). The remaining cases constituted VTE in system of the great main veins of the arm, popliteal/femoral and iliac veins. Complete occlusion of the venous vessels was observed in 82 % of cases. In 40 % of cases of thrombosis localization coincided with the localization of central venous lines (CVL) in the subclavian and/or internal jugular veins. None of the patients had of pulmonary embolism. When analyzing the frequency characteristics was revealed that venous thrombosis by ultrasound diagnosed in 7,3 % (0-24 %) of patients with NHL per year from such who the first time during of the year were receiving treatment in our Centre. A comparative analysis of similar data for 2001/07 and 2008/14 showed an increase in the frequency of diagnoses of thrombotic complications (Chi-square test 4.4; P < 0.05) for patients with NHL receiving treated in hospital in these periods. The average annual growth of detection of this complication for the last 7 years was 1.1 %. Such situation in the last time may be linked with the growth of attention of clinicians to identify thrombotic complications, with the increasing in the number of catheterizations of central and peripheral veins and with the improving of the quality of primary diagnosis of VTE, but no with increasing in the incidence of NHL.
Conclusion. Venous thrombosis in children with NHL ranks first in frequency within the nosology group and in second place in absolute terms among all pediatric patients with malignant tumors. Over the past 7 years was a significant increase in VTE in patients with NHL. VTE in most cases localized in the internal jugular and/or subclavian vein in patient were combined with primary mediastinal tumor localization. Massive mediastinal tumor and CVL in a pool of superior vena cava probably reinforce each other as the VTE risk factors.
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