Search PubMed⌕ Search

Biomedical subjects

M M Horowitz

Publications and source records attributed to M M Horowitz.

At least 127 records · Page 7Linked to original sources
PubMed1990

Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation.

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.

Acute Disease↗
PubMed1990

Graft-versus-leukemia reactions after bone marrow transplantation.

To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic leukemia (ALL) in first remission, and chronic myelogenous leukemia (CML) in first chronic phase. Four groups were investigated in detail: recipients of non--T-cell depleted allografts without graft-versus-host disease (GVHD), recipients of non--T-cell depleted allografts with GVHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants. Decreased relapse was observed in recipients of non--T-cell depleted allografts with acute (relative risk 0.68, P = .03), chronic (relative risk 0.43, P = .01), and both acute and chronic GVDH (relative risk 0.33, P = .0001) as compared with recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect of GVHD. AML patients who received identical twin transplants had an increased probability of relapse (relative risk 2.58, P = .008) compared with allograft recipients without GVHD. These data support an antileukemia effect of allogeneic grafts independent of GVHD. CML patients who received T-cell depleted transplants with or without GVHD had higher probabilities of relapse (relative risks 4.45 and 6.91, respectively, P = .0001) than recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect independent of GVHD that is altered by T-cell depletion. These results explain the efficacy of allogeneic bone marrow transplantation in eradicating leukemia, provide evidence for a role of the immune system in controlling human cancers, and suggest future directions to improve leukemia therapy.

Bone Marrow Transplantation↗
PubMed1990

Current status of allogeneic bone marrow transplantation.

Use of allogeneic BMTs continues to increase. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic BMTs; more than 50% of these were performed in the 3 years, 1985 through 1987. Transplants are effective therapy for leukemia and other hematologic diseases. They are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia, and a variety of immune deficiency disorders. Successful application of BMT is limited by complications such as graft failure, 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 was performed using HLA partially matched related or unrelated donors, with some success. The development of posttransplant 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↗
PubMed1990

Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry.

We studied 2254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase to determine whether graft-versus-leukemia (GvL) reactions are important in preventing leukemia recurrence after bone marrow transplantation. Four groups were investigated; recipients of non-T-cell depleted allografts without graft-versus-host disease (GvHD), recipients of non-T-cell depleted allografts with GvHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants compared with recipients of non-T-cell depleted allografts without GvHD, Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = 0.03), chronic (relative risk, 0.43, P = 0.01), and both acute and chronic GvHD (relative risk 0.33, P = 0.0001). These data support an anti-leukemia effect of GvHD. AML patients receiving identical twin transplants had an increased probability of relapse (relative risk 2.58, P = 0.008) compared to allograft recipients without GvHD supporting an anti-leukemia effect of allografts independent of GvHD. CML patients receiving T-cell depleted transplants without GvHD had a higher probability of relapse (relative risk 6.91, P = 0.0001) than recipients of non-T-cell depleted allografts without GvHD. These data support an antileukemia effect independent of GvHD altered by T-cell depletion. These results indicate that much of the anti-leukemia effect of bone marrow transplants is related to immune factors rather than high-dose chemotherapy and/or radiation.

Bone Marrow Transplantation↗
PubMed1989

Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival.

Transplant outcome was analyzed in 690 recipients of bone marrow transplants (BMTs) for acute lymphoblastic leukemia (ALL) in first (n = 299) or second remission (n = 391). Actuarial 5-year leukemia-free survival was 42% +/- 9% (95% confidence interval) and 26% +/- 6%, respectively; relapse rates were 29% +/- 9% and 52% +/- 8%, respectively. Five-year leukemia-free survival was 56% +/- 18% in children and 39% +/- 10% in adults (P less than .02) transplanted in first remission. In first-remission adults, non-T-cell phenotype, male to female donor-recipient sex-match and graft-v-host disease (GVHD) were associated with decreased leukemia-free survival; inclusion of corticosteroids in the regimen to prevent GVHD was associated with increased leukemia-free survival. Variables associated with decreased leukemia-free survival after second-remission transplants were age greater than or equal to 16 years and relapse occurring while on therapy. Variables associated with increased probability of relapse were similar for first- and second-remission transplants and included GVHD prophylaxis without methotrexate and absence of GVHD. In first-remission transplants, leukocyte count greater than or equal to 50 x 10(9)/L at diagnosis was also associated with increased relapse; in second remission, relapse while receiving chemotherapy was also associated with increased posttransplant relapse. These data emphasize the importance of both disease- and transplant-related variables in predicting outcome after BMT. They may be used to explain differences between studies, design future trials, and identify persons most likely to benefit from BMT.

Adolescent↗
PubMed1989

Susceptibility of hospital-based health care personnel to varicella-zoster virus infections.

Varicella-zoster virus (VZV) transmission poses a major infection risk for health care workers in the hospital environment. Immunologically normal adults who contract varicella have 9 to 25 times the risk of major morbidity or death from infection compared with healthy children. Moreover, varicella infection during pregnancy is associated with a high rate of complications and the risk of the congenital varicella syndrome. To evaluate susceptibility to VZV infection among hospital workers, the employee health service screened 241 personnel for VZV antibody by the indirect fluorescent antibody technique. Overall, 7 (2.9%) of 241 personnel lacked VZV antibody and were therefore presumed susceptible to infection. Susceptibility varied dramatically by age and was significantly higher among persons 35 years of age and younger (7/93 = 7.5%) than among those aged 36 years and older (0/148 = 0%, p = 0.001). Persons 35 years old or younger with a clinical history of chickenpox or herpes zoster were much less likely to lack immunity (3/71 = 4.2%) than those stating they had no history of either (4/11 = 36.4%, p = 0.005). Screening strategies for VZV immunity in hospital employees could be made more efficient by performing serologic tests only on those persons aged 35 years or younger with a negative or uncertain history of the disease. Persons who lack antibody may be considered for preexposure immunization with live attenuated varicella vaccine as an alternative to varicella-zoster immune globulin or enforced absence from patient care after exposure to a VZV-infected patient.

Adult↗
PubMed1989

Risk factors for interstitial pneumonia following bone marrow transplantation for severe aplastic anaemia.

Data from 547 patients with aplastic anaemia who received bone marrow transplants from HLA-identical siblings were analysed to determine factors associated with the risk of interstitial pneumonia (IPn). IPn developed in 92 patients (17%). 37% of cases were associated with cytomegalovirus infection and 22% with other organisms; in 41% of cases no organism was identified. The case fatality rate was 64%; the mortality rate due to IPn was 11%. In multivariate analysis, four factors were associated with an increased probability of interstitial pneumonia: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.8; P less than 0.0008); occurrence of moderate to severe acute graft-versus-host disease (relative risk, 2.2; P less than 0.002); inclusion of total body radiation in the pretransplant preparative regimen (relative risk 2.2, P less than 0.004); and patient age greater than 20 (relative risk 1.7, P less than 0.002). The probability of IPn ranged from 4% for patients with none of these adverse risk factors to 51% (relative risk of 13.4) for patients with all four. The incidence of IPn decreased significantly between 1978 and 1985, paralleling a decrease in the use of total body radiation pretransplant for immune suppression and methotrexate post-transplant for prophylaxis against graft-versus-host disease.

Adolescent↗
PubMed1989

Current status of bone marrow transplantation.

Utilization of bone marrow transplantation as a therapeutic modality continues to increase. More and more institutions are initiating bone marrow transplant programs. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic bone marrow transplants; more than 50% of these were performed in the 3 years, 1985-1987. Transplantation is an effective therapy for acute leukemia; in some instances it is the preferred treatment. In chronic myelogenous leukemia, severe aplastic anemia, and some genetic and immune deficiency diseases, bone marrow transplantation provides the only possibility for cure. Bone marrow transplantation is associated with serious problems such as graft-versus-host disease (GvHD), graft failure, interstitial pneumonitis and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants have been performed using HLA-partially matched related or unrelated donors with some success, the level of which is yet to be determined. The development of acute GvHD (8) and interstitial pneumonitis (9, 10) can often be predicted by risk factor assessment. Special precautions can then be taken for patients at high risk of these complications. In this report, current data from the International Bone Marrow Transplant Registry were summarized and several risk factors affecting outcome were identified.

Anemia, Aplastic↗
PubMed1989

Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results.

Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in 16 of 27 patients with transient initial engraftment but in none of ten patients with no sign of engraftment after the first transplant. The major factors associated with a reduced risk of graft failure were use of radiation for pretransplant immunosuppression and use of cyclosporine rather than methotrexate or T-cell depletion of the donor bone marrow for prophylaxis against graft-v-host disease (GVHD). Among 266 patients prepared for transplantation with cyclophosphamide alone, the risk of graft failure was increased in patients who received previous transfusions and reduced in those who received corticosteroids for previous therapy. Neither cell dose nor administration of donor buffy coat cells affected the probability of engraftment. Although use of radiation in conditioning reduced graft failure, survival was not improved. Posttransplant treatment with cyclosporine and avoidance of pretransplant blood transfusions were associated with improved survival.

Actuarial Analysis↗
PubMed1989

Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry.

A questionnaire comprised of a series of clinical vignettes illustrating potential difficulties in diagnosis, grading and treatment of chronic graft-versus-host disease (GVHD) was completed by 65 bone marrow transplant physicians from 51 transplant centers worldwide. The concordance index (CI) for responses to each question was calculated using the formula CI = 2p-1, where p was the percentage agreement among respondents. Possible responses ranged from 0 (no agreement) to 1.00 (perfect agreement). Responses indicated moderate (CI = 0.55), high (CI = 0.88) and moderate (CI = 0.54) agreement among transplanters for diagnosis, grading and treatment of chronic GVHD, respectively. Disagreement was observed in (1) diagnosis of uncommon manifestations of chronic GVHD; (2) in interpretation of symptoms which occur less than 2 months after transplant; (3) in interpretation of persistent stable symptoms; and (4) in deciding whether to treat chronic GVHD limited to skin. The results point to potential problem areas in designing and interpreting clinical trials to prevent or treat chronic GVHD and highlight the need for improved diagnostic criteria.

Adolescent↗
PubMed1989

Temporal relationships between the major complications of bone marrow transplantation for leukemia.

Data from 3113 patients receiving HLA-identical sibling bone marrow transplants for leukemia were analysed to determine the time course of the major causes of treatment failure. The median interval from transplant to onset of acute graft-versus-host disease (GVHD) was 17 days, interstitial pneumonitis 63 days, and chronic GVHD 111 days. The median interval from transplant to relapse was 3.3 months for patients transplanted in relapse of acute leukemia or blast phase of chronic myelogenous leukemia (CML), 6.4 months when transplants were performed in second or subsequent remission of acute leukemia or accelerated phase of CML, and 7.8 months for patients transplanted during first remission of acute leukemia or while in the first chronic phase of CML. Shorter intervals from transplant to onset of interstitial pneumonitis or chronic GVHD were associated with a significantly lower probability of 2-year survival. The temporal relationships between these complications are displayed graphically and demonstrate the overlapping and competing causes of death following allogeneic bone marrow transplantation.

Adolescent↗
PubMed1988

Duration of immunity after hepatitis B vaccination: efficacy of low-dose booster vaccine.

Although the efficacy of hepatitis vaccine is well documented, the duration of immunity of healthy adults after vaccination is unknown. We studied 245 hospital employees 3 years after primary vaccination with hepatitis B vaccine to determine the prevalence of immunity indicated by levels of antibody to hepatitis B surface antigen of 10 mIU/mL or greater; and to compare the immunogenicity of low-dose intradermal vaccine with standard-dose intramuscular vaccine in persons found to be seronegative. Thirty-eight percent of employees studied had antibody levels less than 10 mIU/mL. Low levels were associated with smoking, older age, and higher body-mass index. Seventy-eight percent of persons with low antibody levels responded to a single booster vaccine. Two micrograms of intradermal vaccine was as effective as 20 micrograms of intramuscular vaccine in inducing an antibody response; however, intradermal vaccine was associated with more local reactions (42% compared with 17%). Many healthy adults will need periodic boosters of hepatitis B vaccine to maintain production of antibody to hepatitis B surface antigen; low-dose intradermal booster schedules may be feasible.

Adult↗