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The plasma cell disorders constitute a heterogeneous group of diseases. Accumulation of knowledge in the field has helped us to understand these diseases better, stage them more precisely, prognosticate more accurately and manage them more effectively. The paradigm shift in the management of multiple myeloma over the last one-and-a-half decades shows no signs of slackening. In addition to novel therapies, better supportive care and high-dose melphalan with autologous hematopoietic stem cells have contributed to this positive outcome. This review summarizes the developments in this sphere in the recent past.

Chronic myeloid leukemia (CML) in Asia has an incidence rather lower than in Western countries yet tends to afflict a younger population. As in the West, imatinib mesylate (IM, Glivec) has supplanted busulphan, hydroxyurea and interferon-alpha as first-line treatment. Its use has resulted in a dramatic decline in the number of hematopoietic stem cell transplantations (HSCT) performed. Although it is expensive, IM induces a complete cytogenetic response in 60-90% of newly diagnosed patients, and up to 10% for those in blastic phase. The standard dose of 400 mg is well tolerated by most patients, although adverse events have been observed, including drug-induced cytopenia. Through the Glivec International Patient Assistance Program, the majority of CML patients has access to IM and can expect prolonged survival, even in the absence of HSCT. However, just as in Western countries, resistance to imatinib has emerged in Asian countries. They will require the novel tyrosine kinase inhibitors (dasatinib, nilotinib) becoming available through either clinical trials or market approval. This review examines the available data on CML in China, Hong Kong, India, the Philippines, Singapore, South Korea, Taiwan and Thailand.

Background: Cancer antigen 125 (CA 125), a widely used tumor marker for monitoring epithelial ovarian cancer, is also found to be raised in non-gynecological tumors and non malignant disease involving peritoneum. We report a case of non-Hodgkin's lymphoma who presented with peritoneal and pleural effusions with a very high level of serum CA 125., Case: Fifty four years female presented with gross ascitis, bilateral moderate pleural effusions, right retroperitoneal mass and a very high serum CA 125 level (4462.60 u/ml). She was initially evaluated to rule out ovarian malignancy but her biopsy from retroperitoneal mass came out to be diffuse large B cell non-Hodgkin's lymphoma., Conclusion: In a female patient with ascitis with high serum CA 125 level, a differential diagnosis of lymphoma should not be overlooked unless cytology comes positive for epithelial carcinoma cells.

We report a case of AML-M1 with 5q aberration at diagnosis. The patient was treated with high-dose chemotherapy (HDCT). After remission induction, he received allogenic peripheral blood stem cell transplantation (PBSCT) from an HLA-match donor brother. The successive follow-up conventional cytogenetics investigations in remission after HDCT and PBSCT revealed cytogenetic remission. The most interesting observation in this case is that relapsed marrow revealed the emergence of an entirely new, highly aberrant, unrelated clone with unusual translocations t(6;17)(p23;p11.2),+8,der(8)dup inv(8)(q23qter), t(10;19)(q26;q13.3) 4½ months after PBSCT. Our findings suggest the possibility of a mutagenic effect of HDCT and myeloablative intense chemotherapy before PBSCT that could have induced a genetic lesion in the recipient's genetically unstable stem cells in an environment of immunosuppression. The highly complex nature of the clone and the rapid clonal evolution indicates the possibility of selective pressure with proliferative advantage.

Background: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients., Methods: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT., Results: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months., Conclusions: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

HHV-6 is a latent herpes virus persisting throughout the adult life of the infected host in an integrated form and is often activated in immunocompromised situations. Detection of HHV-6 DNA in the plasma of an individual indicates the presence of active viral replication in the host. Because lymphomas are known to be associated frequently with host immunosupression, we studied activation of HHV-6 in 98 patients diagnosed with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). HHV-6 activation was documented in 34% of cases of non-Hodgkin's lymphoma and 39% of those of Hodgkin's disease; however, no correlation of activation status with pathological types of Hodgkin's disease and between copy numbers in peripheral blood mononuclear cell DNA and the corresponding plasma DNA was noticeable.

Background: Allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation remains the only modality of treatment that can eradicate a leukaemia clone in the majority of patients with chronic myeloid leukaemia (CML). However, the advent of the targeted molecule imatinib mesylate (formerly STI-571) against the bcr-abl chimeric protein in the disease has brought the issue of managing newly diagnosed CML patients, especially those with available donors, to the crossroads. Although the curative potential of this agent remains unknown, it can produce complete cytogenetic response in > 60% of newly diagnosed patients., Methods: From May 1991 to October 2002, a total of 55 Ph+ CML-chronic phase patients received oral busulphan 16 mg/kg and cyclophosphamide 120 mg/kg i.v. as a conditioning regimen. All patients received human leucocyte antigen (HLA)-identical sibling donor haematopoletic stem cells--bone marrow in 41 patients (74.5%) and peripheral blood stem cells in 14 (25.4%). Post-transplant prophylaxis for graft-versus-host disease included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporin till day +180 in 38 patients (69.1%), while a combination of cyclosporin and methylprednisolone was used in the remaining 17 (29%)., Results: At a median follow up of 48 months (10-144 months), 26 patients (47.3%) are alive. Early mortality (100-day) occurred in 17 patients (30.9%). Acute graft-versus-host disease developed in 37 patients (67.3%), and was grade IV in 6 of them. Chronic graft-versus-host disease developed in 17 patients (30.9%). Relapse occurred in only 2 patients (3.6%) till date. The leukaemia-free survival is 64.3% in the peripheral stem cell group, whereas it is 41.5% in the bone marrow recipient group., Conclusion: Allogeneic BMT appears to result in eradication of CML and ensure disease-free survival in about half the patients. However, efforts should be made to prevent graft-versus-host disease and minimize early mortality.

Purpose: Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points., Patients and Methods: Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy., Results: With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19)., Conclusion: Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.

Reduced-intensity conditioning that harnesses the potential of a graft-versus-tumor (GVT) effect has been proposed as an alternative to conventional myeloablative allogeneic stem cell transplantation. The primary aim is engraftment and this can be achieved with minimal immunosuppression. In this report, we describe the use of such regimens for CML in 17 patients who received human leukocyte antigen (HLA)-matched sibling allografts. Conditioning was with fludarabine, antithymocyte globulin (ATG) and busulfan for the first 11 patients, whereas fludarabine, busulfan and TBI were used for the remaining six patients. Engraftment was prompt in most of the cases. Complications and need for supportive therapy in the immediate post-transplant period were reduced drastically. Only two patients (both in the TBI group) died within the first 100 days. Acute graft-versus-host disease (GVHD) grade II-IV was seen in seven patients. Complications occurred later on. Chronic GVHD was observed in 11/17 patients. Lung infection and GVHD were the major killers. In surviving patients, after a median follow-up of 30 months (range 37-21 months), 6/17 (35.3%) are alive. Five are disease free and one patient is still in relapse even after a second donor lymphocyte infusion. Total treatment time and cost were more than with conventional transplants. We conclude that reduced-intensity transplantation still requires further refinement.

Advanced obstructive colorectal cancer is routinely treated by surgical colostomy. Self-expandable metal stents are a promising alternative. We report the use of an expandable metal stent to relieve colonic obstruction in an elderly lady with advanced colorectal malignancy.

Objective: To study the outcome of oral busulfan and intravenous cyclophosphamide (BuCY 2 regimen) followed by allogeneic bone marrow transplant (BMT) in a cohort of patients with Philadelphia chromosome (Ph+) chronic myeloid leukaemia (CML) in a single centre., Methods: From 1991 to March 1998, a total of 27 consecutive Ph+ CML patients received busulfan 4 mg/kg/day over 4 days and cyclophosphamide 60 mg/kg/day over 2 days followed by infusion of HLA-identical sibling haematopoietic stem cells. All except one (who received peripheral blood stem cells) were given donor bone marrow cells. Post-transplant graft versus host disease (GVHD) prophylaxis included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporine till day +180., Results: With a median follow-up of 30.5 months (1-55+ months), 14 patients (52%) are alive free from relapse. Early mortality was relatively high with 10 patients (37%) dying within first 100 days post-transplant. Acute GVHD developed in 14 patients (52%) inspite of GVHD prophylaxis with methotrexate and cyclosporine; six had grade I/II and eight grade III/IV. Chronic GVHD developed in five of 15 patients who lived beyond 70 days., Conclusion: Allogeneic BMT appears to result in eradication of CML and ensure disease free survival in about half of the young patients. However, efforts should be on to minimise early mortality.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder. Although now multiple treatment options are being available, the optimal treatment of this disease still remains debatable. Inspite of the advent of newer purine analogues, in India recombinant interferon is the only freely available first line treatment. We report our experience of long term remissions in HCL with interferon alpha 2a. Of a total of 35 cases of HCL we were able to treat 19 cases with interferon. Of 18 evaluable cases an overall response of 88.9% was achieved. With a median follow up of 31 months a disease free survival was 83%. Thus with a dose of 3 million units s.c. daily for 6 months at least, we feel that a reasonably good long term remission can be obtained. The cost of the treatment however, is still a deterrent.

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA.

Background: Combination chemotherapy consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B) has been frequently used for the treatment of non-Hodgkin's lymphoma. This randomized study was undertaken to assess the efficacy and toxicity of this regimen when either doxorubicin or epirubicin was used as the anthracycline drug., Methods: Between April 1989 and December 1993, 211 previously untreated patients with intermediate grade and high grade non-Hodgkin's lymphoma were randomized to receive either doxorubicin (n=106) or epirubicin (n=105) with the MACOP-B regimen. These patients were followed through December 1996. Numerous clinical features predictive of response and survival were analyzed. Cardiac and noncardiac toxicity in the two treatment arms were compared., Results: The median age of the patients was 48 years. Complete remission was experienced by 122 patients (58.3%); 62 patients (58.5%) achieved complete remission in the doxorubicin arm and 60 (58.1%) in the epirubicin arm. Response rates, time to treatment failure, relapse data, and overall survival were comparable between the two arms. Morbidity due to mucositis, vomiting, peripheral neuropathy, and cardiotoxicity were also comparable. The overall mortality was 10%. Mortality due to neutropenic sepsis was considerably higher among patients who received epirubicin (10 patients) than among those who received doxorubicin (5 patients). Cardiac evaluation revealed no difference in toxicity between the two arms., Conclusions: Epirubicin was as effective as doxorubicin in terms of patients' responses to therapy. There was no difference in cardiotoxicity between the two treatment arms. However, in this study, the mortality due to neutropenic sepsis was significantly higher among patients treated with epirubicin.

To assess the effect of combination chemotherapy with doxorubicin, bleomycin, viablastine, and decarbazine (ABVD) on gonadal function in patients treated for Hodgkin's disease, we assessed 38 male patients with Hodgkin's disease who were > 15 years of age and in complete remission for the development of secondary sexual characteristics, sexual habits, and fatherhood after treatment. Semen analysis and serum hormone level estimation of follicle-stimulating hormone (FSH), leutinising hormone (LH), and testosterone (T) were done in all cases. Twenty-six patients received ABVD therapy and 12 received a combination of ABVD with COPP or MOPP (cyclophosphamide or nitrogen mustard, vincristine, procarbazine, and prednisone). Radiation of the pelvic region was done in one case. Median time between completion of therapy and assessment of gonadal function was 34 months (range, 12-68 months). Secondary sexual characteristics developed normally in all patients. Azoospermia was seen in one patient from the ABVD group and 10 patients from the COPP/ABVD group (p < 0.001). Serum FSH levels were significantly higher in the COPP/ABVD group than in the ABVD group (23.5 versus 4.7 mlu/ml; p < 0.001) The levels were in the normal range in 23 patients from the ABVD group, as compared to four in the COPP/ABVD group (88.5% versus 33.3%; p < 0.001). Three patients treated with ABVD fathered children post-therapy. We conclude that ABVD is associated with relatively better preservation of gonadal function.

From 1986 to 1994 we treated 26 patients of aplastic anaemia between 6 to 61 years age group with ATG/ALG, Methylprednisone and Oxymethalone. Five had very severe aplastic anaemia, 16 had severe and 5 nonsevere disease. Disease was associated with hepatitis in 5 patients and with pregnancy and drug use in 2 patients each. In others no cause could be ascertained. A total of 31 courses of treatment were given (range 1-3 courses per patient). Nine patients had complete response (34.62%) and 3 had partial response (11.54%) with an overall response rate of 46.16%. Four patients died within 2 months of starting the treatment. The median follow up was 24 months (range 6-102 months) with an overall survival probality of 45% at 2 yr. At the time of evaluation 12 patients have died, 9 are alive disease-free and 5 are alive with disease. The side effects associated with therapy were tolerable and did not require cessation of therapy in any patient. We conclude that ATG/ALG with Methylprednisone and Oxymethalone is beneficial to significant number of patients with aplastic anaemia.

Hepatic veno-occlusive disease (VOD) is the second most common cause of death after autologous bone marrow transplantation (ABMT). A patient with multiple myeloma undergoing ABMT developed classic features of hepatic VOD. He responded to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed remarkable correlation with the severity of VOD and response to therapy.

Philadelphia (ph) chromosome positive chronic myeloid leukemia developed in a patient treated for chronic lymphocytic leukemia after treatment with total body irradiation. The role of radiation in the development of CML is discussed.

Twenty eight patients of myelodysplastic syndrome (MDS) were treated with low dose cytosine arabinoside to study the effect of this treatment modality. All patients presented with a hemoglobin of less than 12 Gm/dl, 4 (15%) had neutropenia with an absolute neutrophil count of less than 500 x 10(6)/L and 18 (65%) had thrombocytopenia of less than 100 x 10(9)/L. The subtypes according to the bone marrow evaluation included 14 patients of refractory anemia with excess blasts (RAEB), 10 refractory anemia with excess blasts in transformation (RAEB-T), and 4 chronic myelomonocytic leukemia (CMML). Five patients (18%) achieved complete hematological response, 10 (36%) had a partial response and 9 (33%) patients had no response. Four patients died early during treatment due to tumor lysis (1 CMML) and hemorrhage (3 RAEB). Seven patients progressed to acute myeloid leukemia (AML) while on therapy and three progressed to AML after completion of therapy. Five patients died of hemorrhage and 3 of septicaemia after achieving an objective response. The mean duration of follow up in these patient was 8 months (range 1 month-3 years). Only 3 patients of RAEB have survived for greater than 2 years. Our data reveals the short term benefit of this mode of therapy and emphasizes the need to develop newer therapeutic approaches.

The purpose of this study was to analyze the outcome of patients who completed therapy for acute lymphoblastic leukemia (ALL) and to study the role of an aggressive induction regimen in preventing post therapy relapses. Four hundred and twenty-two patients with ALL who completed therapy during the period 1975-1991 were followed. Two hundred and sixty patients received the aggressive MCP 841 protocol and 162 patients received various other less aggressive treatment regimens. Patients were followed with periodic examination and complete blood counts. The incidence of post therapy relapse was 27% in the less aggressive protocols and 15% in the MCP 841 protocol (p = 0.001). An higher percentage of relapses was seen in males (p = 0.05) and 89% relapses occurred within two years of stopping therapy. The relapse rate after 5 years of cessation of therapy was 0.59%. In conclusion, aggressive induction therapy is the most crucial factor in predicting relapses following cessation of therapy in ALL patients. However, relapses are unlikely to occur five years post therapy.

This is a retrospective study of Hodgkin's disease in children less than 15 years of age who were registered at Tata Memorial Hospital in India from January 1985 through December 1990. Clinicopathologic characteristics and response were evaluated in 147 patients and survival was calculated in 187. There were 126 boys and 21 girls (6:1). All patients were treated with combination chemotherapy and involved field radiotherapy. The COPP schedule was given to 108 patients. COPP/ABVD to 33, and ABVD to 6. Ninety-three patients (63%) had stage I or II disease and 54 (37%) had stage III or IV disease. B symptoms were observed in 65 patients (56%) and bulky disease in 40 (27%). Histologically, the most common subtype was mixed cellularity, seen in 95 patients (65%). Complete response was observed in 136 (89%), partial response in 6 (4%), and there were 4 treatment-related deaths. Relapse has been observed in 11%. Seven-year actuarial survival was 73% and event-free survival was 64%. Median survival has not yet been reached, with a median follow-up of 36 months.

Purpose: This study is an analysis of our experience with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, in pediatric germ cell tumors (GCTs)., Patients and Methods: The study included all children (age < 16 years) who were registered between May 1988 and May 1993 with a histologically confirmed diagnosis of GCT and received BEP chemotherapy. In addition to the clinicopathological features, the response rate, survival rate, and toxicity were analyzed., Results: There was a total of 56 patients, of whom 22 had an ovarian tumor and 17 each had a testicular or an extragonadal tumor. Histologically, endodermal sinus tumor was the most common type (62%). Tumor markers were increased in 89% (50 of 56). Complete responses were observed in 89.1% (49 of 55) and partial responses in 10.9% (6 of 55) of the evaluable patients. Five-year actuarial survival was 83% and progression free survival was 93%. Median follow-up was 18 months. Median survival is not yet reached. The chemotherapy was well tolerated., Conclusions: From the present report, it is apparent that BEP chemotherapy is very effective and well tolerated in children with GCT. The data probably suggests that conservative surgery, when combined with effective chemotherapy, can result in cure of the majority of children with GCTs.

We evaluated harvested marrow cells for total nucleated cells (27.49 x 10(9)), absolute 'lymphocyte' count (6.29 x 10(9)) and CD 34 positive cells (3.57 x 10(9)). The same parameters were studied after in vitro manipulation to remove RBCs and plasma. Reinfused WBCs contained 12.87 x 10(9) nucleated cells, 4.25 x 10(9) absolute 'lymphocyutes' and 3.34 x 10(9) CD 34 positive cells. The corresponding figures for loss during in vitro manipulation (tubing, RBCs and plasma) are 14.62 (53.18%), 2.04 (32.43%) and 0.23 x 10(9) (6.44%) cells respectively. Therefore CD 34 positivity may be a better indicator of total yield, loss during manipulation and reinfusion of hemopoietic progenitor cells in bone marrow transplantation.

Combination chemotherapy consisting of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisolone and bleomycin (MACOP-B) has been extensively used for the treatment of Non Hodgkins Lymphoma. However, different results have been reported. The aim of this study was to assess the feasibility of administration of this regimen on an out patient basis and to confirm the efficacy of MACOP-B. 51 patients with intermediate--and high--grade lymphoma were treated with this regimen in a single institute study. Numerous clinical features predictive of response and disease free survival were analysed. The Median age was 48 years (range 14-77). Diffuse large cell lymphoma was seen in 65%, diffuse small cleaved in 10% and diffuse mixed in 15%. Eight patients (15%) had Stage I disease, 18 (35%) Stage II, 12 (23%) Stage III and 13 (25%) Stage IV. Complete remission was achieved in 65% of the patients. With a median follow up of 18 months, 40% of the patients are alive at 40 months. Sixty percent of the complete responders are disease free at 40 months. Response rates did not differ significantly for age, sex, stage, histology, bone marrow involvement and extranodal disease. However patients with absence of B' symptoms, non bulky disease at presentation and diffuse large cell histology had a higher percentage of complete remission. Hematological toxicity occurred in 90% and was grade IV in 14% patients. Three patients died of sepsis. Severe mucositis occurred in 40% of the patients. In conclusion, while it is possible to give aggressive chemotherapy at the out patient basis in India we failed to confirm the high response rates as originally reported.

The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. In this study the outcome of multiagent chemotherapy in children treated for germ cell tumor is assessed. Between January 1984 and December 1990, 107 patients were diagnosed to have germ cell tumors. Postsurgical therapy was based on tumor site, stage, and histology. Combination chemotherapy was employed in patients with Stages I and II disease with postoperative raised tumor markers and all patients with Stages III and IV. Between 1984-1988, patients received cisplatin, vinblastin, bleomycin, and methotrexate (PVB-M), and thereafter between 1988-1990, they received bleomycin, etoposide, and cisplatin (BEP). Of 34 patients treated with PVB-M and 27 treated with BEP, the complete remission rate was 40% and 85%, respectively, and the overall survival was 30% at 5 years for PVB-M and 80% at 3 years for BEP. We conclude that etoposide with cisplatin is superior to vinblastin with cisplatin in the treatment of advanced germ cell tumors because of greater efficacy, decreased toxicity, and better compliance in children.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

Primary orbital lymphomas are rare. We report nine such cases (4 with DWDL, 3 with DPDL, 1 with DHL and 1 unclassifiable lymphoma). All patients achieved clinical complete remission (CR). Of those who completed treatment more than a year ago, three continue to be in CR at 17, 24 & 25 months and two are lost to follow up.

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC-CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia-positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC-CML patients developed meningeal leukemia within a median period of 6 months (range 2-11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC-CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.

Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary bladder cancers following prolonged cyclophosphamide therapy are being increasingly reported. We report a case of transitional cell carcinoma of the urinary bladder occurring 12 years after pulse intravenous therapy with cyclophosphamide for Hodgkin's disease. The mechanism of bladder carcinogenesis and the possible role of the uroprotector MESNA in preventing cyclophosphamide induced bladder cancer are discussed.

Six patients of primary lymphoma of breast are presented. All our patients were female with median age of 46 years. Combination chemotherapy was the mainstay of treatment in all the patients. Five patients achieved complete remission of which two relapsed, one had a distant relapse and the other was local. Patient with distant relapse expired after a follow-up of 224 months whereas the one with local recurrence was well controlled with radiotherapy only. The role of combination chemotherapy to decrease the distant relapse and thereby mortality is discussed.

We report two patients with primary plasma cell leukemia (PLC) treated with a single agent, ifosfamide. One patient had a total disappearance of plasma cells (PC) from the peripheral blood and the bone marrow and disappearance of the myeloma protein, is disease free 8 months after completion of treatment, and alive 14 months after diagnosis. The second patient had a partial response with persistence of plasma cells in the bone marrow lasting 7 months, after which she had a frank relapse of the disease. We suggest that ifosfamide may be an active agent in plasma cell malignancies and needs further evaluation in multiple myeloma.

A 37 year old man with symptomatic multiple myeloma diagnosed in April 1968 presented with generalised bony pains, extensive skeletal osteolytic lesions, monoclonal gammopathy and 90 percent atypical plasma cells in the marrow. He was given cyclophosphamide for six months with minimal response and then initiated on melphalan for one year. He was asymptomatic for 15 years thereafter and presented again in 1985 with a relapse of the disease. Over the next four years he was given various combinations of chemotherapy including cyclophosphamide, vincristine, melphalan and carmustine. He responded well on two more occasions only to relapse again. Recently, he has developed a symptomatic relapse with 36 percent plasma cells. This case report highlights the fact that there is a subset of patients with myeloma who survive beyond ten years, but remain symptomatic and respond slowly to chemotherapy.

During 1984-1986, a total of 128 children with acute lymphoblastic leukemia (ALL) were treated with an induction-consolidation regimen consisting of doxorubicin, vincristine, cytosine-arabinoside, and prednisolone. One hundred two (80%) patients belonged to high-risk group. The complete remission rate for all the patients was 91%. The event-free survival at 5 years was 32.0% +/- 23%. On multivariate analysis the event-free survival and disease-free survival was not altered by age, sex, WBC count, platelet count, LDH level, and surface phenotype. Infection due to prolonged marrow aplasia was a common complication, leading to mortality of 8 patients during induction and 33 patients during first remission. The relapse rate has been 36% (42 patients). The predominance of high-risk ALL in the Indian population underscores the need for intensive therapy. Improved supportive care during induction and remission seems essential to decrease therapy-related mortality, leading to improved survival.

In the last decade, 14 patients were diagnosed as having hairy cell leukemia (HCL) at our hospital; five of these were treated with the biological response modifier, recombinant alpha-interferon (IFN), as their initial treatment. Four of these cases showed a complete remission of the disease while one had a good partial response after a few months of therapy. One case is in unmaintained remission while one has relapsed with a just palpable spleen on stopping the drug; two are still on intermittent IFN therapy while one has been lost to follow up. Fever and skin rash were the most common side effects observed but did not warrant reduction of dose or stoppage of treatment. We conclude that IFN is highly effective and well tolerated as initial treatment of HCL in a country like India. Splenectomy will continue to be the first line therapy in the majority of cases but, in certain selected situations, IFN can be an extremely useful alternative.

We report two cases of primary extranodal lymphoma of the prostate, an unusual site for extranodal presentation. The clinical presentation and treatment is discussed.

Twenty-five patients with acute nonlymphoblastic leukemia undergoing 41 cycles of chemotherapy with daunorubicin/cytosine arabinoside (ara-C) or with etoposide/ara-C received metoclopramide (MCP; 0.5 mg/kg 6 hourly i.v.) or MCP (same dose) plus oral lorazepam (1 mg/d) during and 24 hours following the chemotherapy as antiemetic medication. Control of vomiting was achieved is 55% (complete 5%, partial 50%) of the patients receiving MCP alone and in 100 percent (complete 76.1%; partial 23.8%) of those receiving MCP plus lorazepam (p less than 0.001). Eighteen of the 21 patients (85.7%) receiving MCP plus lorazepam opted for the same antiemetic regimen as compared to six of the 20 (30%) receiving MCP alone (p less than 0.01). One patient in each group developed mild sedation during the treatment. It is concluded that oral lorazepam is an effective and safe adjuvant to MCP for the control of vomiting during cancer chemotherapy.

Primary non-Hodgkin's lymphoma of the liver is exceedingly rare and until now only 53 cases have been recorded. Most extranodal non-Hodgkin's lymphomas are in the head and neck region and the gastrointestinal tract. We report a patient with primary non-Hodgkin's lymphoma of the liver and also review the relevant literature.

Four cases of primary non-Hodgkin's lymphoma of the lung are described. Two cases had low and two intermediate grade lymphoma at the time of diagnosis. The patient who had disease for long duration and received pulmonary radiotherapy developed intractable chest infection and died six months after diagnosis; the three patients having short history of disease and treated with surgery and/or chemotherapy have been doing well for 4 to 77 months after the diagnosis. It is concluded that diagnosis of primary pulmonary lymphoma should be suspected in patients with nodular or interstitial lung disease and bronchoalveolar lavage with aspiration cytology should be done to make an early diagnosis.

Aggressive chemotherapy regimens and supportive measures in haemato-oncology patients demand reliable venous access. Experience with this method in India has been limited. During a period of six months, we have used 42 subclavian indwelling catheters and 31 cubital Cavafix long lines. The mean age of patients in the two groups was 32 years and 7 years respectively. Subclavian catheters had a median duration of catheter placement of 46 days (range 4-145) and total 1494 catheter days, while cubital longlines yielded a median duration of insertion of 14 days (range 4-27) and total 508 catheter days. Catheter related complications were infection in 25% of patients, thrombophlebitis in 22%, blockade in 12% and misplacement in 17% in both groups taken together. The patients and families were extremely satisfied with the devices. Our experience supports further use of durable venous access in cancer patients. Implanted central venous catheters should be preferred whenever feasible.

Gonadal functions were evaluated in 92 male patients after treatment for advanced Hodgkin's disease. The patients received six to ten cycles of cyclophosphamide, vincristine, procarbazine, and prednisolone (COPP) chemotherapy. All patients were in remission and were followed for 1 to 17 years (median, 6). Testicular atrophy was noticed in 89 (96.7%) patients. All patients remained azoospermic during the period of follow-up. The testosterone levels did not differ before and after treatment. The follicle stimulating hormone levels rose from pretreatment values (mean +/- standard deviation) of 179.27 +/- 21.99 ng/ml to 578.79 +/- 102.36 ng/ml after the treatment; the rise was significant (P less than 0.001). The luteinizing hormone levels rose from pretreatment values of 106.96 +/- 20.37 ng/ml to 127.37 +/- 32.19 ng/ml after treatment; the rise was significant (P less than 0.05). Testicular biopsy specimens in 19 patients showed germinal aplasia in all cases. It is concluded that six or more cycles of COPP chemotherapy for advanced Hodgkin's disease in men leads to permanent sterility.

Between March 1983 and December 1985, six patients with haematological disorders (four acute nonlymphocytic leukaemias, one chronic phase chronic myeloid leukaemia and one severe aplastic anaemia have undergone allogeneic bone marrow transplantation. Four of the 6 patients are alive and free from disease between 33+ and 55+ months; two patients died due to grade IV acute graft versus host disease (GVHD).