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Biomedical subjects

S J Forman

Publications and source records attributed to S J Forman.

At least 163 records · Page 9Linked to original sources
PubMed1987

Epstein-Barr-virus-related malignant B cell lymphoplasmacytic lymphoma following allogeneic bone marrow transplantation for aplastic anemia.

The development of B cell lymphoma has been reported to occur in recipients of a variety of organ transplants, including some patients who have received an allogeneic bone marrow graft. In this report, we describe a patient with severe aplastic anemia who developed a malignant B cell lymphoplasmacytoid proliferation 48 days after undergoing allogeneic marrow transplantation from her HLA-matched MLC-nonreactive brother. Immunologic studies showed this malignancy to be a mixed polyclonal and monoclonal proliferation in donor cells. Virologic studies documented Epstein Barr infection of the cells. A review of the literature suggests that graft-versus-host disease and treatment of this complication by antithymocyte globulin are related to the development of the EBV-related malignancy in the EBV-infected B cells of the developing bone marrow graft.

Adult↗
PubMed1987

Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.

Acute Disease↗
PubMed1987

Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies.

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty-four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v-host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease-free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.

Acute Disease↗
PubMed1987

Improved results of treatment of adult acute lymphoblastic leukemia.

We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission-induction phase followed by intensive alternating cycles of non-cross-resistant chemotherapy and prolonged oral maintenance therapy. Eighty-one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

Adolescent↗
PubMed1987

Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies.

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16-213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

Acute Disease↗
PubMed1987

Total-body irradiation and high-dose teniposide: a pilot study in bone marrow transplantation for patients with relapsed acute lymphoblastic leukemia.

Inadequate leukemic ablative therapy ending in leukemic relapse is the source of most failures following bone marrow transplantation. Attempting to improve pretransplant leukemic ablative therapy, we report on a pilot regimen that includes teniposide, the principal chemotherapy, and total-body irradiation. Ten patients with acute lymphoblastic leukemia in relapse underwent allogeneic bone marrow transplantation. All patients engrafted. Toxicity, primarily mucositis, was manageable. Two patients have survived for 1547 and 1988 days in continued remission. Eight patients have died: three from sepsis in the immediate posttransplant period, four with recurrent leukemia, and one with chronic graft-versus-host disease and pneumonia. We believe that these results support further trials with teniposide in pretransplant leukemic ablative therapies.

Adolescent↗
PubMed1987

Cytarabine, cisplatin, and etoposide chemotherapy for refractory non-Hodgkin's lymphoma.

A phase II trial of cytarabine, cisplatin, and etoposide was conducted in 38 patients with refractory stage III and IV non-Hodgkin's lymphoma. There were two complete and nine partial responses (32%) among 35 evaluable patients. Response rate in patients with large cell lymphoma was 45%. The dose-limiting toxic effect was myelosuppression in 66% of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis.

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.

Anemia↗
PubMed1986

Polypeptide-specific antibody response to human cytomegalovirus after infection in bone marrow transplant recipients.

Human cytomegalovirus (HCMV) infection continues to be the most important infection occurring after allogeneic bone marrow transplantation (BMT). Although T cell-specific antiviral immunity appears to be necessary for control of the infection, the humoral immune reaction also contributes to a complete immune response. In this paper we report our findings concerning the antibody response to the individual polypeptides of HCMV in patients who had undergone BMT and subsequently had displayed evidence of HCMV infection. Sera obtained from the subjects during and after HCMV viremia were studied by using both a radioimmunoprecipitation assay and an immunoblot assay, and the results were compared with the pattern of antibody response in normal individuals. The results show that the BMT patient can make antibodies to individual proteins of HCMV in a pattern similar to that displayed by persons with natural infection. The polypeptide-specific antibody response present most frequently was directed to proteins of 64 kDa, 50 kDa, and 36 kDa. Some BMT recipients also produced antibody to a wide range of HCMV proteins: 183 kDa, 155 kDa, 130 kDa, 110 kDa, 92 kDa, 86 kDa, 74 kDa, 71 kDa, 69 kDa, 39-44 kDa, 33 kDa, and 29 kDa.

Adult↗
PubMed1986

Bone marrow transplantation for hematologic malignancies in patients aged 30 years or older.

During the past 10 years, 86 patients 30 to 54 years of age with hematologic malignancies were prepared with high-dose radiochemotherapy and received histocompatible bone marrow grafts. Thirty-four of these patients are surviving for 4 months to 9 years (median, 26 months) following marrow transplantation and 32 of them are in continuing complete remission (CR). Disease-free survival is 44% for 37 patients who were in first remission of acute leukemia or in the chronic phase of chronic granulocytic leukemia (CGL), 23% for 39 patients whose leukemia had relapsed at least once before transplantation or who had advanced stages of CGL, and 60% for ten patients who had hematologic malignancies other than leukemia. The median age of the surviving 34 patients is 36 years (range, 30 to 43 years). The incidence of moderate to severe acute graft-v-host disease (GVHD) was 48% and of chronic GVHD, 26%. The major causes of failure were interstitial pneumonia in 31 patients (24 of whom had antecedent acute GVHD) and recurrent leukemia in 12 patients (11 of whom had either never entered a CR or had relapsed at least once with acute leukemia or had progressive CGL before transplantation). Our data warrant further prospective studies in patients with hematologic malignancies who are older than 30 years.

Actuarial Analysis↗
PubMed1986

Synergy between interleukin-2 and a second factor in the long-term growth of human T cells.

It has recently been shown that factors in addition to interleukin-2 (IL-2) are required for the proliferation or differentiation of at least some murine T-cell lines. We have previously shown that conditioned medium from human mononuclear cells stimulated with phorbol ester and staphylococcal enterotoxin A is superior to commercial sources of IL-2 for the long-term growth of human T cells. We have identified in these supernatants a non-IL-2 factor (synergistic factor, SF) which synergizes with JURKAT IL-2 in the long-term growth of human T cells. [3H]TdR incorporation by IL-2-dependent human T cells after growth in IL-2 or SF alone for 14 days was slight, but significant. By contrast, growth in a combination of SF and IL-2 for 14 days stimulated [3H]TdR incorporation 10-20-fold higher, generally equal to the high incorporation measured when cells were grown in the presence of the conditioned medium from which SF was obtained. In a standard 2-day IL-2 assay, there was no correlation between activity and long-term growth-promoting ability. These results suggest that the 14-day assay better discerns the growth-promoting activity of various factors or combinations of factors. The mechanism of this interaction between SF and IL-2 remains to be elucidated. It is clear, however, that T-cell growth factor activity, when assessed by the long-term growth of human T cells, is not due to interleukin-2 alone.

Antigens, Surface↗
PubMed1985

A 64,000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen.

Human cytomegalovirus contains approximately 30 to 35 structural polypeptides. Although antibodies to several of these proteins are made during natural infection, their relationship to T cell recognition of this virus and subsequent control of infection is poorly understood. We have purified one of these proteins (HCMVgp64) that is found in abundance in infected cell lysates in order to delineate the relationship of single viral proteins to the immune response caused by the virus. HCMVgp64 induced T cell reactivity only in individuals with serologic evidence of past infection. In addition, HCMVgp64 elicited similar in vitro immune reactions as the whole virus including T cell proliferation, interleukin 2 production, and receptor expression as well as interferon production. These studies suggest that single proteins of HCMV such as HCMVgp64 are capable of inducing T cell responses and may be important in the development of immune reactivity to HCMV.

Antigens, Viral↗
PubMed1985

Clonal evolution of T-cell prolymphocytic leukemia to a T-large-cell lymphoma. A morphologic and immunologic study.

We describe a patient with T-cell prolymphocytic leukemia who developed a large-cell lymphoma of the T-cell type. The neoplastic cells of the large-cell lymphoma demonstrated the same immunologic phenotype (ER+, Leu-3+, Leu-2-, and HLA ABC+) as the cells of the prolymphocytic leukemia, which indicated a clonal evolution of a T-cell prolymphocytic leukemia into a large-cell lymphoma of the T-cell phenotype.

Aged↗