Highly elevated serum CA 125 in a lady with ascites and retroperitoneal mass--a diagnostic dilemma.

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.

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

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.

Activation of HHV-6 in lymphoproliferative disorders: a polymerase chain reaction-based study.

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.

Allogeneic blood stem cell transplantation in chronic myeloid leukaemia-chronic phase following conditioning with busulphan and cyclophosphamide: a follow up report.

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.

Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?

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.

Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia.

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.

Palliation of malignant colonic obstruction by self-expandable metal stent.

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.

Acute promyelocytic leukemia: all-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone.

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.

Results of allogeneic bone marrow transplant in chronic myeloid leukaemia following conditioning with busulfan and cyclophosphamide.

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--results with alpha interferon therapy.

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.

A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-Hodgkin's lymphoma.

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.

Gonadal function following ABVD therapy for Hodgkin's disease.

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.

Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) with methylprednisone and oxymethalone in aplastic anaemia.

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.

Serum tumor necrosis factor for monitoring response of hepatic veno-occlusive disease to pentoxiphyllin--a case report.

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.

Pulmonary microsporidial infection in a patient with CML undergoing allogeneic marrow transplant.

Very few cases of human microsporidial infection have been reported. The advent of AIDS has changed this. There is increasing recognition that microsporidia are important opportunistic pathogens. However, the number of cases reported in the non-HIV population is small. We report here a case of microsporidial infection in a female patient with chronic myeloid leukemia undergoing allogeneic bone marrow transplantation. There was also an associated fungal infection. The diagnosis could be reached only after postmortem and was confirmed by electron micrography. We suggest that transplant patients are another group of patients who are susceptible to this group of opportunistic pathogens.

Development of Ph positive chronic myeloid leukemia in a patient with chronic lymphocytic leukemia treated with total body irradiation: a rare association.

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.

Low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.

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.

Survival of childhood acute lymphoblastic leukemia: results of therapy at Tata Memorial Hospital, Bombay, India.

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.