R. Gopal

Therapy-Related Leukemia

5 patients developed acute nonlymphocytic leukemia (ANLL) 2–4 years following the use of various cytotoxic agents for other primary disease. Alkylating agents were responsible for development of ANLL in 3 patients while mitomycin-C and methotrexate appear to be linked with leukemia transformation in the remaining 2 patients. 3 patients had a prolonged preleukemic phase preceding ANLL. Pancytopenia observed in 4 of 5 patients favors drug-induced stem cell damage leading to relatively resistant leukemia. Although the incidence of secondary leukemia is not very high, careful use of cytotoxic agents is needed to minimize therapy-linked neoplasms.

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.

Immune dysfunction in non-Hodgkin's lymphoma.

Immune dysfunction seems to be more common in lymphoproliferative disorders wherein the malignant cells originate from the immune system itself. The reactions of Dinitrochlorobenzene (DNCB) and six recall antigens were found to be diminished in patients with non‐Hodgkins lymphomas as compared to control subjects (P < 0.005). The skin reactivity was lost in increasing order in well differentiated, poorly differentiated, and histiocytic types. The depression in delayed hypersensitivity was greater with generalized as compared to localized disease. In angioimmunoblastic lymphadenopathy (AIL), skin tests also showed negative response in 7 of 8 patients. This T‐cell dysfunction in a preneoplastic condition (AIL) suggests early appearance of immunodeficiency and probably a prerequisite for the development of a lymphoma. The serum immunoglobulin levels failed to show any relation with respect to histology or extent of disease. Presumably, the alteration of IgG is secondary to a malignancy.

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.

Treatment results of Hodgkin's disease in Indian children

This is a retrospective study of Hodgkins 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.

Management of Hodgkin's disease in western India.

The authors report a retrospective analysis of 441 patients with Hodgkins disease seen at the Tata Memorial Hospital, Bombay, over a 4‐year period from 1975 to 1978. Clinicopathologic features seem to vary from those reported in the western literature, but are similar to the patterns observed in Africa and South America. Thirty‐three percent of all malignant lymphomas were Hodgkins disease. Histologically, the mixed cell (MC) type (40%) and the lymphocytic predominant (LP) type (24%) were the most common, with 52% of patients presenting in Stages III and IV. The nodular sclerosis (NS) variant occurred in only 11% of the cases. Systemic symptoms were present in 24% of clinical Stage I patients, and increased steadily to 85% in Stage IV patients. Bone marrow biopsies in 242 patients were found to be of little value in Stages I and II. Thirty of 34 patients with positive bone marrow biopsy were in clinical Stages III B and IV, whereas 24 of 34 patients showed MC and LD patterns. Lymphangiography in 104 patients altered the clinical staging of Stages I and II in 27% of the cases with accuracy of 80%. Staging laparotomy performed in 93 patients altered the stage in 45% of clinical Stage I and 62% of Stage II patients. Splenic involvement was common in the presence of systemic symptoms (67%) and MC/LD histology (82%). The incidence of liver involvement was 16% in 15 patients with all, but one, associated with splenic pathology. The clinical stage and histopathologic variants of the disease bear an excellent correlation with a significant impact on treatment responses and total survival. The survival rates for Stage I were 81%, Stage II 76%, Stage IIIA 71%, and Stage IIIB and IV 46% at 48 months. The LP type had the best prognosis with 85% survival at 48 months, whereas the survival in the depleted variety was only 56%. Surprisingly, the MC type did better with a 64% survival, while the nodular sclerosis group had 59% surviving at 48 months.

Mycobacterial Pulmonary Infection Post Allogeneic Bone Marrow Transplantation

Allogeneic bone marrow transplant recipients are prone to pulmonary infections caused by a wide spectrum of organisms. Since the first bone marrow trarnsplatation (BMT) done in 1983 at the Tata Memorial Hospital, we have recently seen the first case of Mycobacterium Fortuitum Chelonae complex among 117 BMT (including 90 allogeneic and 27 autologous) patients. The patient was on immunosuppressants for chronic GVHD post allogeneic BMT done for CML-CP. He developed pulmonary mycobacterial infection 13 months post BMT. Diagnosis was difficult because of the atypical presentation, negative culture reports, and the presence of multiple pathogens due to immunosuppression. In our case the diagnosis was eventually established after examination of material obtained by bronchoscopy. Patient has shown response to antituberculosis drugs after 2 months. This shows the need to consider atypical mycobacterial infection in the differential diagnosis of pulmonary illness in the post allogeneic BMT setting.

Multifocal Extranodal Lymphomas: An Expression of Homing Phenomenon

The present study analyses 27 patients with primary lymphoma involving multiple extranodal sites. Eight patients were found to have multiple extranodal involvement at presentation while in 19 patients, relapse of disease was noticed at a different extranodal site without any other systemic spread. Malignant lymphomas of Waldeyers ring were frequently associated with involvement of gastrointestinal, gonadal or cutaneous lesion. Primary gonadal lymphoma also showed a high incidence of cutaneous, pleura and bone involvement. The homing pattern of mucosa-associated lymphoid cells explains the multifocal extranodal lymphomas with site-specific tropism.

Avascular necrosis of bone in acute lymphoblastic leukemia.

Avascular necrosis of bone (AVNB) is a known complication of systemic adrenocorticosteroid therapy and is thought to be dose related. However, despite the large amount of prednisolone that has been used in the standard treatment of acute lymphoblastic leukemia (ALL), AVNB has rarely been reported with this disease. We have described our experience with an adolescent girl with ALL who developed multifocal AVNB after aggressive chemotherapy, which included high cumulative doses of corticosteroids along with other cytotoxic drugs, some of which have been associated with AVNB. Five similar cases from literature are reviewed. The occurrence of AVNB may become more common in the future with the increasing use of aggressive chemotherapy. Awareness of this possibility will lead to a more rapid diagnosis and early treatment of AVNB.

MALT Lymphoma of Nasal Mucosa Tkeated with Antibiotics

Mucosa associated lymphoid tissue (MALT) lymphomas occur in sites other than the gastrointestinal tract and in the early stages respond to treatment with antibiotics. We report a rare case of nasal mucosal MALT lymphoma which responded to treatment with antibiotics and has since then remained in remission.