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).

V. Raina, All India Institute of Medical Sciences, Institute Rotary Cancer Hospital, should have been included as an author in the published article mentioned above. The authors would also like to correct the spelling of period in the title of the published paper. Treatment of acute lymphoblastic leukaemia in countries with limited resources; lessons from use of a single protocol in India over a twenty year peroidEuropean Journal of CancerVol. 41Issue 11PreviewIn 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. Full-Text PDF

20015 Background: Acute Lymphatic Leukemia in children is a curable disease in the range of 80–90 % in developed Countries by aggressive protocol like BFM, St. Judes’. In developing Countries like ours, patients can’t tolerate those aggressive protocol because of Socio- economic and nutritional factors. The less aggressive Protocol like INCTR (International Network for Cancer Treatment & Research) are suitable in developing Countries like ours. The aim of our study was to see outcome of childhood ALL patient with INCTR protocol and tolerability of the protocol in Indian-asian population. Methods: We treated 480 Children (age range 1–25 years, median age of 11 yrs) with INCTR Protocol at Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India, a tertiary cancer centre from Eastern India during period from April ’99 to Dec ’06. There was female preponderance in the study. Fever 283 (58.9%), lymphadenopathy 211 (43.9%) and haepatosplenomegaly 153 (31.8%) were the major clinical presentation. Forty-three (8.9%) patients were present with hyper Leukocytosis. C-ALL phenotype were the largest group though the incidence of the T-ALL were quite high (27.9%). Results: Remission induction were seen in 446 (92.9%) of the patient. In a follow-up period of 88 months (with an average of 54 months) the disease-free survival ( DFS) was 66.8% (321 patients) with an overall survival of 73.9% (355 patients). The isolated bone marrow relapse was seen in majority of the cases 40 (8.33%) and the major relapse was in maintenance and first 6 months of completion of therapy. The major cause of morbidity was infection 316 (65.8%) followed metabolic complications 81 (16.8%), hemorrhage 52 (10.8%), neurologic 10 (2.08%), hepatitis 6 (1.25%) and pancreatitis 5 (1.04%). The major cause of the mortality was infection 75%(360 patients) followed progressive disease 7.91% (38 patients) and Hemorrhage 5.83%( 28 patients). Conclusions: The data of acute lymphatic leukemia from a developing country is encouraging. The protocol was well tolerated by India- asian population. No significant financial relationships to disclose.

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.

8561 Background: The incidence of retinoblastoma is higher in developing countries than in Europe and United States. In some developing countries, incidence rates per million may be two to six times higher or even more, since very little information is available from rural areas, where retinoblastoma appears to be particularly common. This tumor is characterized by a rapid growth rate. When the disease is detected at early stages and confined to the eye, children have a good prognosis. However, in children with disease that extents beyond the eye, specially to distant parts of the body, the five-year disease free survival is poor. The percentage of children with extraocular disease at diagnosis is much higher in developing countries (approximately 35 to 50%). Methods: The commonest early sign observed in children is leukocoria (cat's eye reflex). This easy sign to recognize offer a unique opportunity to call attention for retinoblastoma when it is still curable. Therefore a National Campaign for early diagnosis of Retinoblastoma in Brazil was initiated in September 2002 with the support of TUCCA (Children Brain Tumor Association) and INCTR(International Network for Cancer and Treatment Research). The campaign includes educational material for the population, for the primary health care workers and for ophtalmologists. A toll free number is available for information to the entire country. The video is on in different public channels in Brazil and was translated to 10 different languages. Results: More than 20 cases were already diagnosed through the campaign Conclusions: The initiative is cost effective. This experience can be a model to other coutries with similar problems. Routine dilated funduscopic examination is recommended. No significant financial relationships to disclose.

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.

Frequencies of the major subgroups of precursor B-cell acute lymphoblastic leukemia in Indian children differ from the West

Annals of the New York Academy of SciencesVolume 918, Issue 1 p. 362-366 Impact of Chemotherapy for AIDS-Related Malignancies in Pediatric HIV Disease CORINA E. GONZALEZ, Corresponding Author CORINA E. GONZALEZ HIV/AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Address for correspondence: Corina E. Gonzalez, M.D., Children's National Medical Center, Pediatric Medicine, Suite 3.5-600, 111 Michigan Ave., N.W., Washington, DC 20010. cgonzalez@cnmc.orgSearch for more papers by this authorMELISSA ADDE, MELISSA ADDE Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorPERDITA TAYLOR, PERDITA TAYLOR HIV/AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorLAUREN V. WOOD, Corresponding Author LAUREN V. WOOD HIV/AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Address for correspondence: Corina E. Gonzalez, M.D., Children's National Medical Center, Pediatric Medicine, Suite 3.5-600, 111 Michigan Ave., N.W., Washington, DC 20010. cgonzalez@cnmc.orgSearch for more papers by this authorIAN MAGRATH, IAN MAGRATH Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this author CORINA E. GONZALEZ, Corresponding Author CORINA E. GONZALEZ HIV/AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Address for correspondence: Corina E. Gonzalez, M.D., Children's National Medical Center, Pediatric Medicine, Suite 3.5-600, 111 Michigan Ave., N.W., Washington, DC 20010. cgonzalez@cnmc.orgSearch for more papers by this authorMELISSA ADDE, MELISSA ADDE Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorPERDITA TAYLOR, PERDITA TAYLOR HIV/AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorLAUREN V. WOOD, Corresponding Author LAUREN V. WOOD HIV/AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Address for correspondence: Corina E. Gonzalez, M.D., Children's National Medical Center, Pediatric Medicine, Suite 3.5-600, 111 Michigan Ave., N.W., Washington, DC 20010. cgonzalez@cnmc.orgSearch for more papers by this authorIAN MAGRATH, IAN MAGRATH Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this author First published: 25 January 2006 https://doi.org/10.1111/j.1749-6632.2000.tb05507.xCitations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume918, Issue1PREVENTION AND TREATMENT OF HIV INFECTION IN INFANTS AND CHILDRENNovember 2000Pages 362-366 RelatedInformation

BACKGROUND: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. PATIENTS AND METHODS: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. RESULTS: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). CONCLUSIONS: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.

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.

Children with HIV who develop NHLs pose a therapeutic challenge due to their preexisting major organ toxicities and susceptibility to infection. Therefore, a protocol utilizing chemotherapeutic drugs that avoided further toxicity and considered to be highly active in the treatment of NHL was designed. The protocol consisted of 3 cycles of therapy, lasting approximately 10 weeks. The primary regimen consisted of high dose cyclophosphamide and methotrexate (MTX) with intrathecal MTX and ara-C. Intensive supportive care in the form of Pneumocystis prophylaxis, IVIG and acyclovir along with G-CSF were incorporated in the treatment plan. AZT and/or ddl were continued throughout chemotherapy in HIV-positive patients. Subsequent cycles of therapy were initiated when the granulocyte count reached 500/cu mm on 2 consecutive days. 9 patients with 10 tumors 1-14 years; (median, 5 years) were treated. The histological diagnosis were: 3. small non-cleaved cell; 3 anaplastic large cell; 3, immunoblastic large cell and 1, plasmacytoid immunoblastic lymphoma. 7 of 9 had CD4 counts <200. 7 patients achieved a CR; 2, PR and 1, no response, 3 partial or non-responders were treated with a relapse regimen consisting of high dose are-C and ifosfamide. Survival ranged from 5-40 months (median, 14 months). 5 of the 9 patients remain alive. 4 patients have died: 2 of HIV-related complications; 1, opportunistic infection; and 1, of progressive disease. Both the primary and the relapse regimen appeared to be effective therapy in the treatment of HIV associated NHLs. Although 3 patients died of HIV related complications or opportunistic infection, none of the deaths occurred during chemotherapy. Overall, the protocol was well tolerated and was successful in prolonging life. A future study alternating both regimens is planned.

Background: 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.Patients and methods: 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.Results: 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.Conclusions: 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.

PURPOSE 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. PATIENTS AND METHODS 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). RESULTS 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. CONCLUSION 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.