[Show abstract][Hide abstract] ABSTRACT: Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10-20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study.
British Journal of Haematology 07/2012; 158(6):749-62. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub-Saharan African centres is presented. Among children (<18 years of age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub-Saharan Africa for fostering high-quality translational research.
British Journal of Haematology 06/2011; 154(6):696 - 703. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the clinical features, prognostic factors and outcome of childhood T-ALL in comparison with B-lineage ALL, treated with a uniform treatment regimen (MCP 841).
Pediatric oncology division of a tertiary care institution in Northern India.
Retrospective analysis of clinical data and survival outcome.
60 children with T-ALL and 139 with B- lineage ALL, and less than 15 years of age treated over 15 years.
T-ALL was observed in 30%. High risk features at presentation (age >10 years, WBC >50,000/mm3, mediastinal mass, and CNS leukemia) were significantly more frequent in T-ALL as compared to B-lineage ALL (P=0.049, P<0.001, P<0.001 and P=0.02, respectively). Fifty five of 60 T-ALL patients (91.7%) achieved complete remission after induction therapy. There were 3 induction and 10 remission deaths while 11 (18.3%) relapsed. The overall survival and event-free survival of T-lineage ALL (61.5±7.6 and 49.9±7.4, respectively) were similar to that of B-lineage patients (68.7±4.7 and 47.1±5.1, respectively). National Cancer Institute risk groups emerged as significant prognostic factor for event free survival only in B-lineage patients.
Even though high risk features were significantly more frequent in T-ALL, survival outcome was similar to that of B-lineage patients. None of the routinely described prognostic parameters significantly impacted survival.
Indian pediatrics 03/2011; 48(10):785-90. · 1.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective analysis of 254 children less than 15 years of age treated with MCP-841 protocol from June 1992 to June 2002 was undertaken to identify the pattern of relapse and determine management lacunae. Two hundred twenty-three (87.8%) children achieved a complete remission of whom 40 (17.9%) relapsed. The mean age of relapsed patients was 6.5 years. The male/female ratio was 9:1. There were 23 (57.5%) isolated bone marrow (BM), 7 (17.5%) isolated central nervous system (CNS), 2 (5%) isolated testicular, 5 (12.5%) BM+testes and 1 each of BM+CNS, CNS+testes, and isolated bone relapses. Twenty-seven children (67.5%) relapsed on-therapy whereas 13 (32.5%) relapsed posttherapy. All 9 CNS relapses occurred on-therapy whereas 5/8 (62.5%) of testicular relapses occurred posttherapy. Lymphadenopathy was the only significant predictor for relapse. High-risk features such as age less than 1 year and greater than 10 years (P=0.047) and white cell count greater than 50.0 x 10(9)/L (P=0.044) were significantly more frequent in patients with early on-therapy relapse than in patients with off-therapy relapse. The overall survival in the entire study cohort was 67+/-3.5%. Modest survival outcome, relapse while on chemotherapy and the higher incidence of CNS and testicular relapse indicate the need for reappraisal of our treatment protocol. There is a need of identifying risk factors and high-risk groups in our set of patients and risk-stratified intensification of chemotherapy in them.
Journal of Pediatric Hematology/Oncology 05/2010; 32(5):370-5. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the results of two phase II trials of ifosfamide in very high risk patients with either partially responsive or recurrent non-Hodgkin's lymphomas. In the first study, in which patients were extremely heavily pretreated (50 per cent had received a very intensive salvage regimen containing very high dose cyclophosphamide), there were two complete responses, two partial responses and one objective (minimal) response among 14 patients treated. Toxicity was acceptable even in this end-stage patient group. We concluded that ifosfamide is an active agent even in patients with tumours resistant to cyclophosphamide. The second trial was a pilot study in 13 patients of a regimen incorporating VP16, ifosfamide/mesna, and high dose ara-C (VIPA). There were four complete responses, five partial responses and two objective responses. Two patients died in complete remission from toxic complications, while a third, with a stably regressed mediastinal mass died after completion of the protocol. While very toxic, we considered that this regimen was highly effective, and have since incorporated a slightly less intensive combination of the same drugs into the primary therapy of high risk patients. Since the primary toxicity of the VIPA combination was myelosuppression, the use of a modified protocol incorporating colony stimulating factors to ameliorate the side-effects and possibly increase dose rate is worthy of further exploration in patients with recurrent B cell tumours.
[Show abstract][Hide abstract] ABSTRACT: Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985, a modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent); five patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16, with intrathecal methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a better overall survival.
[Show abstract][Hide abstract] ABSTRACT: In the 1970s, survival rates after treatment for acute lymphoblastic leukaemia (ALL) in children and young adults (less than 25 years) in India were poor, even in specialised cancer centres. The introduction of a standard treatment protocol (MCP841) and improvements in supportive care in three major cancer centres in India led to an increase in the event-free survival rate (EFS) from less than 20% to 45-60% at 4 years. Results of treatment with protocol MCP841 between 1984 and 1990 have been published and are briefly reviewed here. In addition, previously unpublished data from 1048 patients treated between 1990 and 1997 are reported. Significant differences in both patient populations and treatment outcome were noted among the centres. In one centre, a sufficiently large number of patients were treated each year to perform an analysis of patient characteristics and outcome over time. Although steady improvement in outcome was observed, differences in the patient populations in the time periods examined were also noted. Remarkably, prognostic factors common to all three centres could not be defined. Total white blood cell count (WBC) was the only statistically significant risk factor identified in multivariate analyses in two of the centres. Age is strongly associated with outcome in Western series, but was not a risk factor for EFS in any of the centres. Comparison of patient characteristics with published series from Western nations indicated that patients from all three Indian centres had more extensive disease at presentation, as measured by WBC, lymphadenopathy and organomegaly. The proportions of ALLs with precursor T-cell immunophenotypes, particularly in Chennai, were also increased, even when differences in the age distribution were taken into consideration (in <18-year olds, the range was 21.1-42.7%), and in molecular analyses performed on leukaemic cells from over 250 patients less than 21-years-old with precursor B-cell ALL, a lower frequency of TEL-AML1-positive ALL cases than reported in Western series was observed. The worse outcome of treatment in Indian patients compared with recent Western series was probably due to the higher rate of toxic deaths in the Indian patients, and possibly also due to their more extensive disease - which is, at least partly, a consequence of delay in diagnosis. Differences in the spectrum of molecular subtypes may also have played a role. The higher toxic death rates observed are likely to have arisen from a combination of more extensive disease at diagnosis, co-morbidities (e.g., intercurrent infections), differences in the level of hygiene achievable in the average home, poor access to acute care, and more limited supportive care facilities in Indian hospitals. Toxic death was not associated with WBC at presentation, and hence would tend to obscure the importance of this, and, potentially, other risk factors, as prognostic indicators. Since the prevalence of individual risk factors varies in different populations and over time, their relative importance would also be expected to vary in different centres and in different time periods. This was, in fact, observed. These findings have important implications for the treatment of ALL in countries of low socioeconomic status; it cannot be assumed that risk factors defined in Western populations are equally appropriate for patient assignment to risk-adapted therapy groups in less affluent countries. They also demonstrate that heterogeneity in patient populations and resources can result in significant differences in outcome, even when the same treatment protocol is used. This is often overlooked when comparing published patient series.
European Journal of Cancer 07/2005; 41(11):1570-83. · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82-88% of all NHLs. The proportions of chronic lymphatic leukemia (4-6%), mantle cell lymphoma (MCL, 3-5%), and plasmacytoma (2-4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6-7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3-5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.
[Show abstract][Hide abstract] ABSTRACT: In the past, treatment results in Indian children with ALL have been poor, primarily due to inadequate chemotherapy and supportive care, but perhaps reflecting differences from Western countries in the pattern of subtypes. In an attempt to improve survival, we have used a more intensive treatment protocol, MCP841, and examined prognostic factors.
Five hundred thirty previously untreated patients < 25 years of age with ALL were entered on study at the Tata Memorial Hospital, Mumbai. Treatment consisted of three successive induction cycles, consolidation and six maintenance cycles. CNS prophylactic therapy consisted of cranial irradiation (2000 cGy) for patients above two years and high-dose cytarabine for patients less than two years. The total treatment duration was two years.
Most patients had hepatosplenomegaly (80%) and or lymphadenopathy (79%) and 21% were of T-cell immunophenotype, but very few (1.3%) had CNS disease. CR was achieved in 484 (91.3%) patients and 145 (29.9%) patients relapsed. There were 36 induction deaths and 49 remission deaths, but the toxic death rate was significantly lower after 1990. In patients treated since 1990, three risk groups could be discerned: 1) WBC < 60,000 per mm3 and no lymphadenopathy (77% event-free survival (EFS) at five years): 2) WBC < 60,000 per mm3 with lymphadenopathy (53% EFS) or, WBC > 60,000 per mm3 and Hb 6 gm/dl or above (48% EFS): and 3) WBC > 60,000 per mm3 and Hb below 6 gm dl (16% EFS). In a multivariate model, only WBC, Hb and lymphadenopathy were significantly associated with EFS (P < 0.01).
The CR and EFS rates achieved represent a significant improvement over previous results at this institution. Bulky extramedullary disease was an important risk factor in this series, but age and WBC alone inadequately defined risk groups, suggesting that prognostic factors may vary in different world regions.
Annals of Oncology 03/1999; 10(2):167-76. · 6.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the updated results of an intensive treatment protocol for children (< 18 years) and adults (> or = 18 years) with advanced B-cell lymphomas. The protocol consists of two chemotherapy regimens: A, consisting of cyclophosphamide, doxorubicin, vincristine and high-dose methotrexate (CODOX-M), and B, consisting of ifosfamide, etoposide, and high-dose cytarabine (IVAC). Both cycles included intrathecal chemotherapy (cytarabine or methotrexate). Patients received a total of four cycles in the following sequence: A, B, A, B. Sixty-six previously untreated patients, enrolled before October 1996, were included in the present analysis. Of these, 55 had Burkitt's or Burkitt's-like lymphoma and 11 had diffuse large B-cell lymphoma. There were 53 males ad 13 females; 40 were children and 26 were adults (age range, 3 to 57 years). To date, 61 patients have achieved a complete response to therapy. Two patients subsequently relapsed, but one of these is a long-term survivor after further therapy and a bone marrow transplant. The event-free survival rate is 85% at I year and beyond. The median potential follow-up period is 48 months (range, 12 to 96 months) for patients remaining in complete remission. Neutropenia occurred in 98% of cycles and infection in 46% of A cycles and 50% of B cycles, but the duration was shortened in B cycles by the administration of granulocyte colony-stimulating factor. Positive blood cultures were observed in 21% of A cycles and 28% of B cycles, and there have been three toxic deaths. These results are better than those achieved with an earlier version of CODOX-M, suggesting that the addition of the IVAC regimen is responsible for the improved results. The similarity of the outcome in children and adults, however, confirms our previous observation that, at least in adults younger than 60 years with Burkitt's or Burkitt's-like lymphomas, treatment with regimens similar to those used in children is warranted.
[Show abstract][Hide abstract] ABSTRACT: In the past, the results of the treatment of non-Hodgkin's lymphomas (NHL) in Indian children have been poor, due to inadequate chemotherapy and poor supportive care. In an attempt to overcome these problems, we conducted a clinical trial in Bombay with a new protocol, MCP842.
Seventy-four previously untreated patients < 25 years were entered on study at the Tata Memorial Hospital, Bombay. Patients with lymphoblastic lymphoma (LL) (38) without bone marrow involvement and all patients with small noncleaved cell lymphoma (SNCL) (18) and large cell lymphoma (LCL) (18) were eligible. Treatment consisted of alternating cycles of two regimens, A and B. Patients with St. Jude stages I and II received six cycles, and those with stages III or IV received eight cycles. A cycles included cyclophosphamide, adriamycin, vincristine and ara-C, and B cycles, etoposide, vincristine, methotrexate, ifosfamide and mesna.
Complete response was achieved in 67 (91%) of patients. Event free survival (EFS) for all patients was 58%; 68% for patients with SNCL and LCL combined, and 48% for patients with LL. There was no significant difference in EFS by histology (LL versus non-LL), or stage. There were nine (12%) toxic deaths, two during induction and seven in patients in remission; six occurred in patients with LL.
These results are better than past results in Bombay. Unlike earlier CCG protocols, in which the outcome between patients with LL and non-LL differed, this was not so in MCP842. Even patients with extensive LL without bone marrow disease received only eight cycles of therapy, suggesting that short duration therapy is curative in as many as half of such patients--an important observation in a country with limited resources.
Annals of Oncology 10/1997; 8(9):893-7. · 6.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups.
Seventy-two patients (39 adults and 33 children) were treated with protocol 77-04 between 1977 and 1985. All patients, except those with resected abdominal disease, received 15 cycles of a combination of cyclophosphamide (CTX), doxorubicin (ADR), prednisone (PRED), vincristine (VCR), high-dose methotrexate (MTX), and intrathecal (IT) therapy. Forty-one patients (20 adults and 21 children) were treated with protocol 89-C-41, which has been used since 1989. High-risk patients received four alternating cycles (with a total duration of 12 to 15 weeks) of an intensified version of protocol 77-04 without PRED (CODOX-M), and a new drug combination consisting of ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC). Low-risk patients received three cycles of the CODOX-M regimen. High-risk patients were randomized to either receive or not receive granulocyte-macrophage colony-stimulating factor (GM-CSF).
Event-free survival (EFS) in protocol 77-04 was 56% at 2 years and beyond. EFS in protocol 89-C-41 was 92% at 2 years and beyond. GM-CSF was associated with increased thrombocytopenia.
Adults and children with SNCL have a similar prognosis when treated with the same chemotherapy. EFS in high-risk patients has been markedly improved by including IVAC in protocol 89-C-41, and excellent results can be achieved with only four cycles of therapy. In protocol 89-C-41, GM-CSF was not beneficial.
Journal of Clinical Oncology 04/1996; 14(3):925-34. · 17.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16% of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. Since July 1985, we have treated 39 previously untreated pediatric NHL cases younger than 16 years of age (mean, 7.6 years) with a new protocol consisting of alternating cycles: regimen A comprised cyclophosphamide, high-dose ara-C, Adriamycin and vincristine; regimen B consisted of ifosfamide, methotrexate and VP16, with intrathecal methotrexate. Diagnoses included 20 abdominal masses, 16 peripheral lymphadenopathies and 6 bony lesions. Histopathology according to the working formulation revealed 21 cases of small non-cleaved lymphoma, 6 lymphoblastic, 5 large-cell and 7 unclassified diffuse lymphomas. Responses were complete in 31 cases (82%) and partial in 4 cases (10%), and no response was obtained in 4 cases (8%). Overall survival was 82% in limited disease and 60% in extensive disease at 28+ months. This short-term ifosfamide-containing regimen proved its efficacy, with results matching those of other regimens used in the United States and Europe.
Cancer Chemotherapy and Pharmacology 02/1989; 24 Suppl 1:S20-3. · 2.57 Impact Factor