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Biomedical subjects

M M Horowitz

Publications and source records attributed to M M Horowitz.

At least 91 records · Page 5Linked to original sources
PubMed1994

Report from the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry--North America.

Bone marrow transplants are an effective treatment for many life-threatening diseases. Considerations for use include potential for cure, availability of a suitable donor, feasibility of using autologous stem cells, and risks of transplant-related mortality. Not addressed in this article, but also important, is consideration of the relative efficacy of conventional therapy in specific settings. The IBMTR and ABMTR offer a unique resource for examining the role of allogeneic and autologous transplants in cancer treatment.

Actuarial Analysis↗
PubMed1993

Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose.

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus-leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.

Adult↗
PubMed1993

Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase.

We analyzed the outcome of 450 HLA-identical sibling bone marrow transplants for chronic myelogenous leukemia (CML) in chronic phase performed between 1985 and 1990 and reported to the International Bone Marrow Transplant Registry (IBMTR). All patients received either hydroxyurea (n = 292) or busulfan (n = 158) to treat their CML before transplant. The median interval between diagnosis and transplant was 10 months (range, 1 to 191). Patients treated with hydroxyurea had a higher probability (95% confidence interval) of leukemia-free survival (LFS) at 3 years than those treated with busulfan (61% [51% to 70%] v 45% [36% to 55%], P < .0003). Probability of LFS was also higher in patients transplanted within 1 year of diagnosis (61% [53 to 68%] v 47% [38% to 57%], P < .001). After adjustment for patient and transplant covariables in a multivariate analysis, prior chemotherapy and duration of disease pretransplant were independently associated with LFS. These data support the use of hydroxyurea rather than busulfan and transplant within 1 year of diagnosis for patients with CML and an HLA-identical sibling.

Actuarial Analysis↗
PubMed1993

Outcome after allogeneic bone marrow transplant for leukemia in older adults.

OBJECTIVE: To determine whether age over 40 years is associated with adverse outcome after allogeneic bone marrow transplantation for leukemia. DESIGN: A retrospective analysis of outcome after bone marrow transplants for leukemia reported to the International Bone Marrow Transplant Registry (IBMTR) among recipients 30 through 39 years, 40 through 44 years, 45 through 49 years, and 50 years of age and older. SETTING: Transplantations performed in 138 institutions worldwide and reported to the IBMTR. PATIENTS: A total of 2180 recipients of HLA-identical sibling bone marrow transplants for leukemia, divided into four cohorts based on age: 30 through 39 years (n = 1282), 40 through 44 years (n = 527), 45 through 49 years (n = 291), and 50 years and older (n = 80). MAIN OUTCOME MEASURES AND RESULTS: Incidence of leukemia-free survival, graft-vs-host disease, and relapse was comparable among the four age cohorts. Patients with advanced leukemia aged 45 years or older had a slightly higher risk of treatment-related mortality, and the 45- through 49-year-old cohort had a higher risk of interstitial pneumonia. CONCLUSIONS: These data indicate that among leukemia patients over 30 years of age at the time of allogeneic bone marrow transplantation, increasing age into the fifth decade does not adversely affect outcome after transplants from HLA-identical siblings.

Adult↗
PubMed1993

Methotrexate, cyclosporine, or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia?

Optimal prophylaxis of graft-versus-host disease (GVHD) is controversial. We compared efficacy of three posttransplant immune suppressive regimens in 2,286 recipients of HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia (ALL) in first remission, acute myelogenous leukemia (AML) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase. Six hundred forty received methotrexate, 977 received cyclosporine, and 669 received combined cyclosporine and methotrexate. In children, the three regimens resulted in similar outcomes. In adults, cyclosporine and methotrexate had comparable risks of acute and chronic GVHD. Compared with methotrexate, cyclosporine was associated with less interstitial pneumonia (relative risk [RR] = 0.6; P < .001), less treatment-related mortality (RR = 0.6; P < .001), more relapses (RR = 1.6; P < .05), and less treatment failure (relapse or death from any cause; RR = 0.7; P < .001). Different effects were observed in different leukemias. In ALL, the rate of leukemia relapse was increased with cyclosporine versus methotrexate, with no effect on other outcomes. In AML and CML, interstitial pneumonia, treatment-related mortality, and treatment failures were decreased with cyclosporine, with no increase in relapse. Similar analyses comparing cyclosporine plus methotrexate with cyclosporine alone showed that adults receiving the combination had less acute GVHD (RR = 0.5; P < .001), less chronic GVHD (RR = 0.7; P < .01), and less interstitial pneumonia (RR = 0.7; P < .001). Treatment failure (RR = 0.8; P < .05) was marginally reduced. Separate analyses in ALL and AML showed less acute GVHD with combined therapy, but no significant effect on other outcomes. In CML, acute GVHD, interstitial pneumonia, treatment-related mortality, and treatment failure were decreased with combined therapy.

Adolescent↗
PubMed1993

Human herpesvirus-6 (HHV-6) infection in allogeneic bone marrow transplant recipients: evidence of a marrow-suppressive role for HHV-6 in vivo.

Sixteen adults were studied for the first 100 days after allogeneic bone marrow transplant to assess the pathogenic role of human herpesvirus-6 (HHV-6) infection in patients with unexplained febrile illnesses. HHV-6 was directly isolated from the blood of 6 patients. Analysis of the clinical courses of these 16 patients revealed otherwise unexplained posttransplant marrow suppression in 5 patients. Idiopathic marrow suppression occurred more frequently in patients with concurrent HHV-6 viremia (4/6) than in those from whom HHV-6 was not isolated from peripheral blood (1/10, P < .05). An etiologic role for the virus was also supported by isolation of HHV-6 from the bone marrow of all 4 patients at the time of marrow suppression and by in vitro colony-forming unit (cfu) assays that demonstrated that HHV-6 could inhibit cfu-granulocyte-macrophage and burst-forming unit-erythroid growth from human bone marrow. By restriction enzyme mapping, all clinical isolates were type B, suggesting that bone marrow transplant recipients may be preferentially infected with and reactivate this HHV-6 subtype. This study implicates HHV-6 as a novel cause of bone marrow suppression in marrow transplant recipients.

Adult↗
PubMed1993

Results of bone marrow transplants from human leukocyte antigen-identical sibling donors for treatment of childhood leukemias. A report from the International Bone Marrow Transplant Registry.

PURPOSE: Bone marrow transplantation is an effective treatment for leukemia. Cures are possible in 20-80% of transplant recipients depending on the stage of leukemia at the time of transplant. The antileukemia efficacy of transplants result from high-dose chemotherapy and/or radiation given pretransplant and from immune-mediated effects of the graft. RESULTS: Success of the procedure is limited by transplant-related complications, including graft rejection, graft-vs.-host disease and interstitial pneumonia. Five-year leukemia-free survival ranges from approximately 25% for children transplanted with advanced leukemia, to > 60% in those transplanted in first remission of acute leukemia or first chronic phase of chronic myeloid leukemia. CONCLUSIONS: Candidates for transplant include children failing conventional therapy and, possibly, those with early leukemia characterized by features predicting a poor response to conventional therapy.

Actuarial Analysis↗
PubMed1993

Report from the International Bone Marrow Transplant Registry and the North American Autologous Bone Marrow Transplant Registry.

The Statistical Center of the IBMTR/NAABMTR has expanded its role from collecting data on allogeneic and syngeneic transplants to the area of autologous bone marrow and blood cell transplantation given to support high-dose therapies for cancer. In diseases such as acute leukemia for which both allogeneic and autotransplants are performed, direct comparisons of outcomes of these therapies are now possible. The large number of cases that has accrued rapidly into the NAABMTR (over 9,000 since 1989) will allow us to use sophisticated statistical techniques to determine potential benefits and disadvantages in the rapidly growing area of autotransplantation.

Asia↗
PubMed1993

1993 progress report from the International Bone Marrow Transplant Registry. Advisory Committee of the International Bone Marrow Transplant Registry.

The International Bone Marrow Transplant Registry is an organization devoted to scientific research in BMT. More than 230 transplant teams worldwide contribute detailed information about recipients of allogeneic and syngeneic BMT for study. Results of analyses are published in medical journals and presented at national and international scientific meetings (more than 60 publications and more than 500 presentations in the past 4 years). This collaborative research program has grown rapidly with more than 2000 cases reported annually. This report summarizes results of several recent investigations and reviews the state of BMT in leukemia and aplastic anemia.

Anemia, Aplastic↗
PubMed1993

Anti-pan T lymphocyte ricin A chain immunotoxin (H65-RTA) and methylprednisolone for acute GVHD prophylaxis following allogeneic BMT from HLA-identical sibling donors.

Six patients (five children < or = 12 years old and one young adult) underwent allogeneic BMT (not T lymphocyte-depleted) from sex-matched HLA-identical siblings. GVHD prophylaxis consisted of methylprednisolone (30 mg/m2) and anti-pan T lymphocyte ricin A chain immunotoxin (H65-RTA) (0.1 mg/kg) administered daily for 12 consecutive doses. H65-RTA was initiated at day +5 (n = 4) or day +2 (n = 2). All patients engrafted. Despite receiving the planned GVHD prophylaxis, all patients developed moderate to severe acute GVHD; five patients developed Grade III/IV GVHD. Four patients died 34 to 78 days post-transplant; GVHD was a contributory cause of death in each case. H65-RTA as used in this study was ineffective for the prophylaxis of acute GVHD.

Adult↗
PubMed1993

Alternative donor transplants for leukemia. Scientific Advisory Committee of the International Bone Marrow Transplant Registry.

We analyzed transplant outcome in more than 2,500 recipients of alternative donor and HLA-identical sibling transplants. These data indicate: (1) results of alternative donor transplants are inferior to HLA-identical sibling transplants; (2) zero HLA-antigen disparate unrelated and one HLA-antigen disparate related donors have comparable results; (3) amongst unrelated donors, zero and one HLA-antigen disparity has comparable results; and (4), amongst related transplants, two HLA-antigen disparate transplants fare worse than one HLA-antigen disparate transplants. These data should be useful in deciding when to use an alternative donor and selecting the best donor.

Bone Marrow Transplantation↗
PubMed1992

Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy.

About 30% of adults with acute lymphoblastic leukemia (ALL) and 20% to 40% of children and adults with acute myelogenous leukemia (AML) never achieve remission, even with intensive chemotherapy. Most die of resistant leukemia, often within 6 months or less. In this study of 126 patients with resistant ALL or AML, allogeneic bone marrow transplants from HLA-identical siblings produced remissions in 113 of 115 (98%) evaluable patients. The 3-year probability of leukemia-free survival was 21% (95% confidence interval, 15% to 29%). Leukemia-free survival was similar in ALL (23%, 12% to 40%) and AML (21%, 14% to 31%). Only 3 of 27 patients at risk relapsed more than 2 years posttransplant.

Adolescent↗
PubMed1992

Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s.

OBJECTIVE: To identify changes in practice and outcome of bone marrow transplants for leukemia in the 1980s. DESIGN: Comparison of key explanatory and outcome variables in five 2-year cohorts, from 1980 through 1981 to 1988 through 1989, using a large database of detailed clinical information. PATIENTS: Recipients (7788) of bone marrow transplants for acute lymphoblastic, acute myelogenous, or chronic myelogenous leukemia reported to the International Bone Marrow Transplant Registry, Milwaukee, Wis, by 185 transplant teams worldwide. RESULTS: Linear increases occurred during the periods 1980 through 1981 to 1988 through 1989 as follows with 95% confidence intervals: (1) transplants for chronic myelogenous leukemia from 14% +/- 2% to 35% +/- 2%; (2) transplants from unrelated donors from 1% +/- 1% to 7% +/- 1%; (3) preparative regimens without radiation from 3% +/- 1% to 30% +/- 2%; and (4) use of methotrexate plus cyclosporine to prevent graft-vs-host disease from 2% +/- 1% to 55% +/- 2%. Among recipients of human lymphocyte antigen-identical sibling bone marrow, the 2-year probability of treatment-related mortality decreased by 6% to 22%. The probability of relapse decreased from 46% +/- 6% to 38% +/- 6% in intermediate leukemia but did not change appreciably in early or advanced leukemia. Probabilities of leukemia-free survival improved from 51% +/- 4% to 57% +/- 3% in early leukemia, from 28% +/- 4% to 36% +/- 5% in intermediate leukemia, and from 12% +/- 4% to 18% +/- 5% in advanced leukemia. A separate analysis of a homogenous population of patients indicated that improvements in outcome in the 1980s were due to improvements in transplant practice rather than improved patient selection. CONCLUSIONS: Modest increases in leukemia-free survival rates occurred after human lymphocyte antigen-identical sibling bone marrow transplants in the 1980s. Improvements were due primarily to reductions in treatment-related mortality with little or no change in relapse risk. More effective antileukemia strategies and continued reductions in treatment-related toxic effects are needed.

Adult↗
PubMed1992

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

Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) has a poor prognosis when treated with conventional chemotherapy. We analyzed the outcome of 67 HLA-identical sibling bone marrow transplants (BMTs) for Ph1-positive ALL reported to the International Bone Marrow Transplant Registry (IBMTR). Twenty-one of 67 (31%) transplant recipients survived in continuous complete remission more than 2 years after transplant. Two-year actuarial probabilities (95% confidence interval) of leukemia-free survival were 38% (23% to 55%) for 33 patients transplanted in first remission, 41% (23% to 61%) for 22 patients transplanted after relapse, and 25% (9% to 53%) for 12 patients failing to achieve remission with conventional chemotherapy. These data indicate that transplants are effective treatment for Ph1-positive ALL.

Adolescent↗
PubMed1992

Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers?

There is substantial evidence that the volume of medical procedures in a hospital has an inverse relationship with mortality. We analyzed data for 1313 recipients of HLA-identical sibling bone marrow transplants for early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in first chronic phase) to determine whether transplant outcome differed in small and large centers. Transplants were performed in 86 bone marrow transplant centers active between the years 1983 and 1988, which participated in the International Bone Marrow Transplant Registry. Twenty-one (24%) centers performed five or fewer allogeneic transplants per year during the study period; five (6%) performed more than 40 per year. After adjustment for differences in patient and disease characteristics, the relative risks of treatment-related mortality (1.53, P less than .01) and treatment failure (1.38, P less than .04) were higher among patients who received transplants at centers doing five or fewer transplants per year than among those at larger centers. Among patients receiving transplants in centers performing more than five transplants a year, there was no statistically significant correlation between number of transplants and outcome.

Adult↗
PubMed1992

Increasing utilization of allogeneic bone marrow transplantation. Results of the 1988-1990 survey.

OBJECTIVE: To determine the pattern and frequency of allogeneic bone marrow transplantation from related and unrelated donors from 1988 to 1990. DESIGN AND SETTING: Survey of 342 institutions in 47 countries. MEASUREMENTS: Numbers of patients receiving bone marrow transplantation for specific disease categories at institutions with active allogeneic bone marrow transplant programs. MAIN RESULTS: Patients (14,745) received allogeneic bone marrow transplantation between 1988 and 1990; of these, 1153 (8%) were from unrelated donors. Reasons for transplantation were acute leukemia (47%), chronic myelogenous leukemia (27%), lymphoma and other malignancies (10%), severe aplastic anemia (9%), and other nonmalignant diseases (7%). The number of allogeneic bone marrow transplants per million persons differed among countries, averaging 7.7 per million in North America and 5.7 per million in western Europe. CONCLUSIONS: The use of allogeneic bone marrow transplantation continued to increase at a rate of more than 600 additional patients and 25 new transplant teams annually. This rise is due in part to increasing use of unrelated volunteers as donors. Resources allocated for transplants vary widely among countries.

Bone Marrow Transplantation↗