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Biomedical subjects

M M Horowitz

Publications and source records attributed to M M Horowitz.

At least 109 records · Page 6Linked to original sources
PubMed1992

Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome.

Data for 595 patients with severe aplastic anemia receiving HLA-identical sibling bone marrow transplants were analyzed to determine the effect of pretransplant conditioning and graft-versus-host disease (GVHD) prophylaxis on outcome. Transplants were performed between 1980 and 1987 and reported to the International Bone Marrow Transplant Registry. Three conditioning regimens (cyclophosphamide alone, cyclophosphamide plus limited field radiation, and cyclophosphamide plus total body radiation) were studied; none was associated with superior long-term survival. Three GVHD prophylaxis regimens (methotrexate, cyclosporine, and methotrexate plus cyclosporine) were studied. Recipients of cyclosporine with or without methotrexate had a significantly higher probability of 5-year survival (69%, 95% confidence interval 63% to 74%) than patients receiving methotrexate only (56%, 49% to 62%, P less than .003). Higher survival with cyclosporine resulted from decreased risks of interstitial pneumonia (P less than .0002) and chronic GVHD (P less than .005). Additional risk factors adversely associated with survival included infection pretransplant (P less than .004), use of parous or transfused female donors (P less than .005), older patient age (P less than .005), and 20 or more pretransplant transfusions (P less than .006). These data may prove useful in planning randomized clinical trials and in identifying patients at high-risk of treatment failure.

Adolescent↗
PubMed1992

Current status of allogeneic bone marrow transplantation.

Use of allogeneic bone marrow transplants continues to increase. During the 36-year period between 1955 and 1990, more than 33,000 patients received allogeneic bone marrow transplants; more than 45% of these were performed during the 3 years 1988-1990. Transplants are effective therapy for leukemia and other hematologic diseases. It is widely considered that transplants are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia and a variety of genetic, metabolic and immune deficiency disorders. Successful application of bone marrow transplantation is limited by complications such as graft failure, graft versus host disease GVHD and interstitial pneumonia and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants were performed using unrelated or HLA-partially matched related donors with some success. Development of post-transplant complications can often be predicted by risk factor assessment. In this report, current data from the IBMTR are summarized and several risk factors affecting outcome identified.

Anemia, Aplastic↗
PubMed1992

Report from the International Bone Marrow Transplant Registry.

The number of allogeneic BMTs performed worldwide continues to increase. In addition, the characteristics of patients, donors, and selected treatments are changing. In BMT for leukemia during the 1980s there was a marked increase in transplants for early disease, the use of unrelated donors, and utilization of preparative regimens without radiation. Although treatment-related mortality declined during this period, there was only a modest decrease in relapse rates, indicating the need for more effective antileukemia strategies. The IBMTR collects data from many centers, and, as a consequence, it is uniquely suited to examine clinical situations in which patient accrual at a single institution would be insufficient for a study to be performed. In such analyses, BMT was shown to be an effective treatment for Ph1-positive ALL. Patients tended to have earlier relapses and lower probabilities of LFS than Ph1-negative ALL but the differences were not statistically significant. BMT was also shown to be effective in patients with acute leukemia failing to ever go into remission, most of whom would die within the first 6 months following diagnosis. The IBMTR is a premier example of international scientific collaboration. Its success is a consequence of the desire of investigators throughout the world to combine their clinical data for statistical analysis in order to accelerate and improve patient care.

Adolescent↗
PubMed1992

Cancer after bone marrow transplantation. IBMTR and EBMT/EULEP Study Group on Late Effects.

Cancer may be serious late effect of marrow transplantation. Radiation, chemotherapy, immunosuppression and the original disease for which transplantation was performed may predispose to the development of cancer. 116 of 9732 patients reported to the IBMTR (International Bone Marrow Transplant Registry) have developed a new malignancy. Late effects were evaluated by the EBMT-EULEP (European Bone Marrow Transplant-European Late Effect Project) Late Effect Study Group in 147 patients surviving 6 years and 79 patients surviving more than 10 years. New malignancies developed in 11 of these patients. Lymphomas and leukemia comprised 73 cases reported to the IBMTR and one case reported to the EBMT-EULEP study. Tumors of the skin, oropharynx, vulva vagina and cervix prevailed in 41 patients with solid tumors. The distribution of malignancies is similar to that observed in organ transplant patients not given radiation or chemotherapy and suggests immunosuppression as a major contributory factor. In dogs the incidence of malignancies was studied after either chemotherapy or total body radiation in various regimens and marrow transplantation. Both chemotherapy and radiation shortened tumor-free survival in comparison to untreated dogs. Higher doses, larger fractions and shorter treatment schedules enhanced earlier tumor development. Soft tissue sarcomas and thyroid carcinoma were most frequent in treated, mammary carcinoma in untreated dogs. In treated dogs deaths from cancer were observed starting at the age of 5 years as compared to untreated dogs at the age of 9 years. The data from animal experiments indicate that the incidence of solid tumors in marrow transplant patients may still rise in the coming decades.

Animals↗
PubMed1992

Transplants in ALL.

Explore the source record for details and available documents.

Bone Marrow Transplantation↗
PubMed1992

Progress report from the International Bone Marrow Transplant Registry.

The International Bone Marrow Transplant Registry receives and analyses detailed information contributed by more than 200 transplant teams worldwide. This collaborative research program has grown rapidly; there are now more than 15,000 cases in the database. This progress report summarizes the current status of bone marrow transplantation, the results of recent investigations and studies planned for the coming year.

Anemia, Aplastic↗
PubMed1992

What determines who develops graft-versus-host disease: the graft or the host (or both)?

Considerable experimental data suggest that most, if not all, recipients of conventional (non-T cell-depleted) HLA-identical sibling transplants are likely to develop graft-versus-host disease (GVHD). This is because all donor-recipient pairs are likely to be disparate for numerous non-HLA antigens and because these grafts contain substantial numbers of donor T cells. However, about one-third to one-half of recipients of this type of transplant have little or no GVHD. Here we review recent data in humans suggesting that others factors, like the ability of the host to modulate GVHD reactivity of immune competent cells in the graft, may explain lack of GVHD in some persons. This concept may have implications for preventing and treating GVHD in humans.

Animals↗
PubMed1992

Therapy decisions in leukemia.

Complex factors determine how physicians select between alternative therapies. We conducted a survey of 352 leukemia experts to determine consensus regarding optimal treatment for leukemia and to identify factors correlated with therapy decisions. The study evaluated both general treatment policies and recommendations for specific clinical situations. Responses of chemotherapy, allotransplant and autotransplant experts were compared. Although responses of these groups were similar for general treatment policies, recommendations for specific cases differed substantially. Interestingly, responses of the three groups to some clinical situations also differed from conclusions of several published studies examining these issues. These data suggest that experts may discount published results in favor of personal experiences, perceptions of the best treatment strategy (based on published data or not) or available resources.

Adult↗
PubMed1992

Progress in allogeneic bone marrow transplantation for acute lymphoblastic leukemia in the 1980's: a report from the IBMTR. The International Bone Marrow Transplant Registry.

Among patients with ALL and irrespective of disease state at transplant, highly significant improvements in treatment-related mortality, relapse and leukemia-free survival were observed during the 1980's. Although these results are encouraging, further reductions in treatment-related toxicity and posttransplant relapse are needed to achieve additional advances in the 1990's.

Bone Marrow Transplantation↗
PubMed1992

Second HLA-identical sibling transplants for leukemia recurrence.

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.

Adolescent↗
PubMed1991

T-cell depletion of HLA-identical transplants in leukemia.

We analyzed the effects of T-cell depletion on the outcome of HLA-identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk [RR] 0.45; P less than .0001) and chronic (GVHD) (RR 0.56; P less than .0001). However, it increased graft failure (RR 9.29; P less than .0001). Leukemia relapse also was increased. In first remission acute leukemia or chronic phase chronic myelogenous leukemia, leukemia relapse was 2.75 times more likely after T-cell-depleted transplants (P less than .0001). T-cell depletion increased the risk of treatment failure (RR 1.35; P less than .0003) and decreased leukemia-free survival. We also studied controllable variables associated with outcome of T-cell-depleted transplants. The unique findings were that among recipients of T-cell-depleted transplants for early leukemia, radiation doses greater than or equal to 11 Gy (RR 0.54; P less than .01), dose rates greater than 14 cGy/min (RR 0.56; P less than .002), and additional posttransplant immune suppression with cyclosporine alone (RR 0.53; P less than .0006) or cyclosporine plus methotrexate (RR 0.36; P less than .01) were associated with fewer treatment failures. Use of monoclonal antibodies rather than physical techniques for T-cell depletion (RR 2.01; P less than .03) and fractionated radiation (RR 1.69; P less than .05) were associated with increased treatment failure and lower leukemia-free survival. These data may be useful in designing strategies to improve results of T-cell-depleted transplants.

Adolescent↗
PubMed1991

Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission.

OBJECTIVE: To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. DESIGN: Retrospective comparison of two cohorts of patients. SETTING: Chemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide. PATIENTS: Patients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987. MAIN RESULTS: Similar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% CI, 33% to 43%) with chemotherapy and 44% (CI, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; CI, -3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related. CONCLUSIONS: These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.

Adolescent↗
PubMed1991

Use of a clinical data registry to evaluate medical technologies. Experience from the International Bone Marrow Transplant Registry.

We reviewed the 18 disease-specific evaluations that used the data base of the International Bone Marrow Transplant Registry to determine the effectiveness of alternative strategies for bone marrow transplant. We identify 17 treatment variables that physicians can control and report the associations between these variables and five clinical endpoints: stable engraftment, graft-versus-host disease, development of interstitial pneumonia, relapse, and disease-free survival. We also suggest policies to promote active participation in establishing and operating a registry.

Bone Marrow Transplantation↗
PubMed1991

Duration of response to intramuscular versus low dose intradermal hepatitis B booster immunization.

OBJECTIVE: To determine the duration of the immune response to plasma-derived hepatitis B vaccine among healthcare workers responding to booster doses of intradermal (ID) or intramuscular (IM) vaccine in 1986 and those with protective levels of antibody to hepatitis B surface antigen (anti-HBs) in 1986 without booster vaccine. Both groups received a primary hepatitis B vaccine series 24 to 36 months earlier. DESIGN: Cross-sectional follow-up study two years later of an inception cohort defined in 1986. SETTING: An academically affiliated metropolitan county hospital. PARTICIPANTS: Group 1: Hospital employees responding to booster doses of hepatitis B vaccine given ID or IM in 1986 due to low anti-HBs levels. Forty-one (82%) of 50 eligible persons were evaluated. Group 2: Persons not receiving booster vaccine in 1986 due to protective levels of anti-HBs. A random sample of 95 persons was drawn from a pool of 152 participants with protective levels in 1986. Sixty-five (68%) of 95 contacted persons were restudied. RESULTS: In 1988, 14 (64%) of 22 previous ID responders had anti-HBs levels greater than or equal to 10 milli-international units (mIU)/mL, compared with 17 (89%) of 19 IM responders (p = .055). The 1988 geometric mean titer of IM recipients was 66.4 +/- 4.5 mIU/mL and of ID recipients was 20.7 +/- 7.4 (p = .04). None of 65 Group 2 subjects' anti-HBs titers dropped below 10 mIU/mL by 1988. CONCLUSIONS: Plasma-derived hepatitis B vaccine recipients with anti-HBs levels greater than or equal to 10 mIU/mL at 24 to 36 months after primary immunization are likely to maintain these levels two years later. The diminished durability of the antibody response together with the increased rate of local side effects associated with the ID injection route may limit its applicability as an alternative to using IM booster doses of hepatitis B vaccine.

Follow-Up Studies↗
PubMed1991

Autotransplants in acute leukaemia.

The data we review indicate that in adults with ALL in first remission intensive chemotherapy and radiation given before a transplant is more effective in eradicating leukaemia than current chemotherapy. This is not so in adults with AML in first remission where more intensive therapy does not reduce the likelihood of relapse. Furthermore, leukaemia relapse because of re-infused leukaemia cells is an important issue in autotransplants for ALL. Whether re-infusing leukaemia cells would be important in AML were more effective pretransplant therapy developed is unknown. Presently, there appears to be little sense to test in vitro approaches to remove leukaemia cells in autotransplants for AML because efficacy cannot be evaluated. (A randomized trial is an exception but would not be expected to show a difference.) Another conclusion is that attempts to induce GVHD in autotransplant recipients, such as by using cyclosporine post-transplant (Jones et al, 1989), are more likely to succeed in AML than ALL since the impact of GVHD is substantially greater (Horowitz et al, 1990). However, the GVHD-related antileukaemia effect in AML is associated with chronic GVHD whereas cyclosporine treatment of autotransplant recipients results in acute GVHD. Also, attempts to separate clinical and antileukaemia effects of GVHD were unsuccessful (Sullivan et al, 1989). Another caution is that in AML we detected an immune antileukaemia effect distinct from GVHD (termed GVL) only after HLA-identical sibling transplants. Since GVL was absent in twins it is unlikely to operate after autotransplants. In summary, there is sense in studying autotransplants in adults with acute leukaemia in first remission. However, there are currently no convincing data that autotransplants are superior to current therapy. More intensive treatment seems effective in ALL; the focus should be on increasing the antileukaemia efficacy of pretransplant therapy and on attempts to remove leukaemia cells from the graft. In AML, there is no evidence that more intensive therapy is more effective. This problem needs resolution before evaluating attempts to remove leukaemia cells from the graft. The best place to test new pretransplant regimens is in twins and recipients of HLA-identical sibling transplants without GVHD. The data and ideas we review and discuss should be useful in planning clinical trials.

Bone Marrow Transplantation↗
PubMed1991

Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion.

Results of 470 bone marrow transplants from related donors other than genotypically HLA-identical siblings (alternative related donors) were analysed to identify factors associated with transplant outcome and to determine whether T cell depletion improved results. As compared to 3648 transplant from HLA-identical siblings, alternative related donor transplants were associated with increased graft failure, increased acute graft-versus-host disease (GVHD), and lower disease-free survival. The likelihood of adverse outcome correlated with increasing donor-recipient HLA-disparity. In multivariate analysis of alternative related donor transplants, donor age greater than or equal to 30 years, (relative risk [RR] 1.7, p less than 0.006), intermediate and advanced leukemia (RR 1.5 and 1.6, p less than 0.01 and p less than 0.003), infection pretransplant (RR 1.7, p less than 0.005) and 2- and 3-locus donor-recipient HLA-disparity (RR 1.3, p less than 0.04) were associated with increased risks of treatment failure. The 2-year probability of leukemia-free survival after alternative related donor transplants (n = 43) with none of these adverse prognostic features was 44% (95% confidence interval 28-59%) compared to 56% (95% confidence interval 52-59%) for similar patients receiving HLA-identical sibling transplants (n = 868, univariate p less than 0.03). T cell depletion increased graft failure and decreased acute GVHD after alternative related donor transplants but did not improve leukemia-free survival.

Bone Marrow Transplantation↗