Tapan K. Saikia

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 Hodgkins 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 Hodgkins 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.

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.

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

Summary: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.

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

Combination chemotherapy consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP‐B) has been frequently used for the treatment of non‐Hodgkins 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.

Characterisation of blast cells during blastic phase of chronic myeloid leukaemia by immunophenotyping--experience in 60 patients.

The blast cell population of 60 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were analyzed with a panel of monoclonal antibodies to determine the cell surface antigen phenotypes. In addition, cytochemical stains periodic acid Schiff (PAS), myeloperoxidase (MP), Sudan black B (SBB) and terminal deoxynucleotidyl transferase (TdT) were also utilized for subtyping. Nineteen cases (31.6%) expressed lymphoid phenotypes characteristic of common ALL cells and one case with extramedullary lymph node crisis expressed T-cell surface phenotypes. Thirty cases (50%) expressed solely myelomonocytic surface antigens with significant TdT activity in three. Cytochemical stains contributed to recognize only 57% of these myeloid blasts. Seven cases (11.7%) were with a mixture of heterogenous group of cells expressing phenotypic characteristics for various haemopoietic cells of different lineage--five of them from the cells of non-lymphoid series (myelomono-erythromegakaryocytic series) and the other two with cells from both lymphoid and myeloid series. Additionally, in two cases (3.3%), the precursor cells reacted only with the erythroid monoclonals. Finally, in one case, the blast cells remained unclassified due to nonreactivity with any of the monoclonals used but expressed significant TdT positivity. The response to uniform vincristine and prednisolone (V + P) therapy has shown that lymphoid blast crisis cases were highly responsive in contrast to the cases with non-lymphoid blast crisis (complete remission rate 86 vs 21.4%). The results confirm the evidence of multilineage blast crisis involving either single or mixed haemopoietic differentiation pathway and the utility of having phenotypic characterisation for designing protocols for chemotherapy in the CML patients at the time of blast crisis.

Anterior chemotherapy in esophageal cancer

Front loading chemotherapy using methotrexate (200 mg/m2) alone or methotrexate (200 mg/m2) with cisplatin (20 mg/m2 daily for 5 days) was used in epidermoid carcinoma of esophagus. Evaluation after two courses showed objective response of 50% or greater in 48% of patients with metbotrexate alone. Response rate was increased to 76.2% with addition of cisplatin to methotrexate. Small lesions (less than 10 cm) showed better response as compared to advanced cases. Therapy was generally well tolerated and good palliation was obtained even after the first course. Postchemotherapy treatment either with surgery or radiotherapy was tolerated without any major complications. The data confirm the short‐term usefulness of initial chemotherapy with methotrexate and cisplatin in esophageal cancer. Results of prolonged follow‐up will help to evaluate the role of front loading chemotherapy on long‐term survival. Cancer 56: 1502‐1506, 1985.

Fluorescence in situ hybridization: a highly efficient technique of molecular diagnosis and predication for disease course in patients with myeloid leukemias.

The accuracy of cytogenetic diagnosis in the management of hematological malignancies has improved significantly over the past 10 years. Fluorescence in situ hybridization (FISH), a technique of molecular cytogenetics, has played a pivotal role in the detection of unique sub-microscopic chromosomal rearrangements that helped in the identification of chromosomal loci, which contain genes involved in leukemogenesis. We studied the feasibility and sensitivity of the FISH technique for molecular analysis of translocations markers, t(9;22) and t(15;17) for accurate molecular diagnosis and for monitoring the disease in 21 patients with chronic myeloid leukemia (CML) who received interferon-alpha and/or chemotherapy (7 patients), bone marrow transplantation (14 patients), and 14 patients with acute promyelocytic leukemia (APL) who received all-trans-retinoic acid (ATRA) and/or chemotherapy. We also applied conventional karyotyping (CK) for identification of t(9;22) and t(15;17) at diagnosis. All CML cases had a Ph; t(9;22) and except for two cases all APL had t(15;17). The FISH studies on CML marrows in complete cytogenetic remission (CCR) (100% Ph- by CK) achieved by IFN-alpha, showed 0-2.5% of cells with BCR-ABL fusion in first cytogenetic remission (Controls, range 0.5-1.5%). Repeat follow-up FISH studies could be done in two cases in remission, which demonstrated 0-10% of cells with BCR-ABL fusion. Evaluation of Ph positive status of CML marrow at diagnosis by CK (100% Ph+ cells) and FISH (80-92% BCR-ABL fusion) pointed the existence of dormant clone of normal residual hematopoietic cells along with actively proliferating clones of Ph positive cells. Fluorescence in situ hybridization analysis of post-BMT CML marrows in CCR (0% Ph+ mitoses) could detect MRD with range of 1-6%. Among 14 patients, 9 who showed percentage of BCR-ABL positive cells (0.0-1.5%) almost similar to normal controls, 6 patients had comparatively good prognosis (disease-free survival 7-14 months). Of five patients with residual leukemic cells in the range of 2-6%, 4 relapsed within a period of 3-24 months. Fourteen APL patients in CCR [100% t(15;17) negative cells by CK] were evaluated by FISH to check the presence of residual leukemic cells. In these patients FISH could efficiently detect 1-14.5% of residual cells with PML-RARA (patients mean MRD 5%, controls mean MRD 3.5%, P=.02). Since the time of FISH analysis, 5 to 7 patients with higher fraction of leukemic cells (5-11%) relapsed within a short period (1-7 months). On the contrary, 5 of 7 patients with either absence or low percentage of PML-RARA positive cells remained in complete remission for 11-24 months. Our data show that FISH has a potential to detect and measure the fraction of aberrant malignant cells in remission marrows, induced by BMT in CML and chemotherapy in APL. These findings encourage the investigations on a large scale to merit its potential for identification of patients at high risk. In the present studies, FISH on interphase cells also demonstrated its efficiency in the molecular diagnosis by its ability to detect BCR-ABL and PML-RARA fusion in CML with masked/variant Ph and t(15;17) negative APL, respectively. The efficiency of technique in molecular diagnosis was also proved in one of the CML patients who progressed to myeloid blastic phase where interphase FISH could identify an extra BCR-ABL fusion on both chromosomes 9 indicating insertion of BCR into ABL and its duplication.

Karyotypic findings as an independent prognostic marker in chronic myeloid leukaemia blast crisis

Fifty-three patients with Ph positive chronic myeloid leukaemia in blastic phase were studied. Additional abnormalities were found in 29 (55%) patients and were more common in myeloid (64%) than lymphoid (45%) blast crisis. The most frequent were +Ph (32%), +8 (28%), +19 (19%), +20 (9%) and +21 (9%). i(17q) (9%) was associated with thrombocytopenia (5/5) and basophilia (2/5). The incidence of additional abnormalities was higher in patients treated with busulphan (70%) than hydroxyurea (44%). No significant differences were noted in the mean values of the clinical and haematological findings recorded at blast crisis between patients with only Ph positive (PP) cells and those with additional abnormalities (AP + AA). Univariate analysis identified karyotypic findings as an independent prognostic marker indicating its significance in assessing the response to therapy and survival after the onset of transformation.

A prospective, randomized double-blind trial comparing metoclopramide alone with metoclopramide plus dexamethasone in preventing emesis induced by high-dose cisplatin

We observed 50 patients receiving high‐dose cisplatin‐based chemotherapy in a prospective, randomized double‐blind trial. One group received metoclopramide (MCP) alone (total dose, 6 mg/kg), whereas the other group was given dexamethasone (DMS) (total dose, 60 mg) in addition to MCP. The patient characteristics of the two groups were comparable, confirming satisfactory randomization. Multivariate regression analysis failed to show any statistical significance in the antiemetic response between the two treatment groups. However, female patients receiving Adriamycin (Adria Laboratories, Columbus, OH) concurrently and obese persons exhibited more vomiting. The overall antiemetic response rate was 66%. Because the side effects were minimal, a higher dose of MCP is expected to improve emetic control without increasing toxicity. The use of a 36‐hour assessment period in our study gave more meaningful data. An exponential increase in the dose of MCP is probably required, with respect to weight, to obtain the same antiemetic efficacy.

Pattern of subtypes of acute lymphoblastic leukemia in India

Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.