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Biomedical subjects

S J Forman

Publications and source records attributed to S J Forman.

196 records · Page 11Linked to original sources

Reversal of acute ("malignant") myelosclerosis by allogeneic bone marrow transplantation.

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor.

Acute Disease↗

Immunoblastic sarcoma of T-cell versus B-cell origin: I. Clinical features.

Within the Lukes-Collins classification system of malignant lymphoma, a tumor of large transformed lymphocytes, termed immunoblastic sarcoma (IBS), is described. This morphological type would have been included within the "histiocytic" category of Rappaport. Immunoblastic sarcoma may be of B-lymphocytic or T-lymphocytic origin. Since differences or similarities of these two variants have not yet been described, we reviewed the case histories of 35 such patients, all of whom had immunologic marker studies performed. Nineteen patients had T-cell IBS (T-IBS), whereas 16 had B-cell IBS (B-IBS). Median age for both groups was approximately 50 yr. A history of prior immune disorder was found in 31% of B-IBS and 16% of T-IBS cases. Prior lymphoproliferative malignancy was noted in 21% of T-IBS and 13% of B-IBS patients. All T-IBS patients first presented because of lymphadenopathy, whereas 56% of B-IBS cases initially presented because of extranodal disease. Systemic "B" symptoms were common in both. Similarly, most patients had widespread disease (stage III or IV) at diagnosis. Clinically suspected hepatic (p = 0.05) and retroperitoneal node (p = 0.01) involvement were more often found in T-IBS. Forty-one percent of T-IBS patients demonstrated polyclonal hypergammaglobulinemia, a finding seen in no B-IBS patient (p = 0.02). Although not statistically significant because of small numbers of patients, data on therapy and survival suggest that IBS of B-cell type may be successfully treated with aggressive, multiagent chemotherapy, while alternative approaches appear warranted in T-cell disease.

Adult↗

Histochemical demonstration of terminal deoxynucleotidyl transferase in leukemia.

White blood cells from 22 patients with leukemia and lymphoma were studied for the presence of terminal deoxynucleotidyl transferase with a peroxidase-antiperoxidase method. The enzyme was detected in leukemic cells of 5 patients with acute lymphoblastic leukemia and 1 patient with chronic myelogenous leukemia, whereas 16 patients with different forms of leukemia or lymphoma were negative for this enzyme. Comparative studies using a biochemical and an indirect immunofluorescence assay revealed complete concordance between these three methods.

Animals↗

Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia.

Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia.

Acute Disease↗

Hemolytic anemia in Wilson disease: clinical findings and biochemical mechanisms.

Two patients with Wilson disease who presented with severe hemolytic anemia are described. One was noted to have unusually high serum copper levels (369 micrograms/100 ml). A review of similar such patients in the literature suggests that, rather than having a low serum copper, patients with hemolysis accompanying Wilson disease have very high serum copper levels. For this reason, in vitro studies of the toxic effects of copper on erythrocytes were undertaken. It was found that, although copper does not have a major direct inhibitory effect on glycolytic enzymes such as hexokinase, the metal does inhibit hexokinase as a consequence of its interaction with oxyhemoglobin. However, such inhibition does not appear to be a major factor in copper-induced hemolysis. On the other hand, the addition of the lipid antioxidant butylated hydroxyanisole (BHA) suppresses hemolysis in copper-treated cells. These experiments suggest that the primary toxic effect of copper is mediated through its oxidant actions on membrane phospholipids rather than through its potential inhibitory effects on intracellular enzymes.

Adult↗

Positive Coombs test in Hodgkin's disease: significance and implications.

To clarify the clinicopathologic characteristics of Coombs' positivity in Hodgkin's disease, the records of 71 cases were reviewed. The direct Coombs test was positive in seven. Mean age of the seven was 22 yr (range 11-33). All were males. All had extensive disease (pathologic stage III or IV) and six had systemic (B) symptoms. Four had mixed cellularity; three had nodular sclerosis. The positive Coombs test was detected at original diagnosis in three and at time of relapse in four. Although all were anemic, only three had evidence of overt hemolysis. The antibody responsible for Coombs positivity was characterized in three and fulfilled the criteria for IgG anti-It. The presence of a positive direct Coombs test in the patient with Hodgkin's disease suggests active and advanced disease. The presence of IgG anti-It may represent a unique antibody in the Coombs-positive hemolytic anemia associated with Hodgkin's disease.

Adolescent↗

Heterogeneity of response and survival in diffuse histiocytic lymphoma after BACOP therapy (bleomycin, doxorubicin, cyclophosphamide, vincristine, prednisone).

Diffuse 'histiocytic' lymphoma (DHL) is heterogeneous pathologically, consisting of four subtypes within Lukes-Collins; large-cleaved (LC), large non-cleaved (LNC), immunoblastic sarcoma of B cells (B-IBS), and immunoblastic sarcoma of T-cells (T-IBS). This heterogeneity is also recognized in the Cooperative Working Formulation on non-Hodgkin's lymphoma. Prior studies have suggested clinical heterogeneity of DHL as well, although conclusions were hampered by small numbers, and lack of therapeutic uniformity. We treated 57 patients with advanced DHL, using BACOP: 22 LNC, 16 T-IBS, 13 B-IBS, six LC. Complete remission rate for LNC was 64 per cent (14/22); B-IBS was 54 per cent (7/13); LC was 33 per cent (2/6); T-IBS was 25 per cent (4/16). (p = 0.10). Median survival for LNC was 27.8 months, B-IBS was 25.9, LC was 14, T-IBS was 12.0. The survival was significantly shorter for T-IBS patients when compared to the others (p = 0.01). By multi-variate analysis, histologic subtype (p = 0.02), age (p = 0.03), and stage (p = 0.06) were significant and independent prognostic variables in predicting survival. We conclude that LNC may respond the most favourably to BACOP, whereas alternative regimens appear necessary for patients with T-IBS.

Antineoplastic Combined Chemotherapy Protocols↗

Allogeneic bone marrow transplant in pediatric patients with high-risk hematopoietic malignancies early in the course of their disease.

PURPOSE: The purpose of this study was to investigate the role of bone marrow transplant (BMT) early in the course of disease for pediatric patients with high-risk leukemia using a preparatory regimen of fractionated total body irradiation (FTBI) and etoposide (VP-16). PATIENTS AND METHODS: Those studied were 33 patients aged < or =18 years with either acute leukemia in first complete remission (CR) (n = 29) or chronic myelogenous leukemia (CML) in first chronic phase (n = 4) who received 1,320 cGy FTBI followed by high-dose VP-16 (60 mg/kg) as a preparatory regimen for BMT from matched sibling donors. Patients with acute leukemia included 18 with acute nonlymphocytic leukemia (ANLL), one with biphenotypic acute leukemia (BAL), and 10 with selected "high-risk" acute lymphocytic leukemia (ALL). Patients with ALL were selected for a high risk for recurrence: those who failed standard remission induction chemotherapy, had a t(9;22) or t(4;11) chromosomal translocation, or had certain clinical high-risk features. RESULTS: At the time of analysis, 28 patients are alive, all of them in continued complete remission for 1.1-7.8 years (median, 5.3 years; mean, 4.9 years). The Kaplan-Meier projected event-free survival (EFS) is 84.5% at 7 years, and the actuarial recurrence hazard is 6.5%. All surviving patients have a performance status of >80%. CONCLUSION: This result of early BMT in a two-institution study of pediatric patients with hematopoietic malignancies suggests that (a) matched sibling allogeneic BMT after conditioning with FTBI and high-dose VP-16 is an excellent treatment for pediatric patients with high-risk leukemia, and (b) children may have a better prognosis than adults treated with allogeneic BMT. Larger multiinstitutional cooperative trials for pediatric patients are needed to confirm this result.

Adolescent↗