A. A. Rimm

FACTORS ASSOCIATED WITH INTERSTITIAL PNEUMONITIS AFTER BONE-MARROW TRANSPLANTATION FOR ACUTE LEUKAEMIA

Data from 176 patients with acute leukaemia given allogeneic marrow transplants between Jan. 1, 1977, and Dec. 31, 1980, and reported to the International Bone Marrow Transplant Registry were analysed retrospectively for prognostic factors associated with the development of interstitial pneumonitis (IPn). The overall incidence of IPn was 20% (36/176), and the disease was fatal in 21 of the 36 cases (58%). Three of more than thirty prognostic factors studied seemed to be associated with a low risk of IPn--pretransplant total body irradiation at a dose-rate less than or equal to 5.7 cGy/min, when compared with higher dose-rates (p less than 0.001); post-transplant immunosuppression with cyclosporin-A, when compared with methotrexate (p less than 0.0003); and transplantation of cells from female donors into female recipients (p less than 0.0005). The low dose-rate of total body irradiation and the use of cyclosporin-A were considered as independent variables, but were confounded to the extent that it was not possible to determine if one or both factors were associated with a decreased incidence of IPn.

BONE-MARROW TRANSPLANTATION FOR ACUTE LEUKAEMIA IN FIRST REMISSION

Between 1978 and 1980 133 patients with acute myelogenous leukaemia were given allogeneic bone-marrow transplants from an HLA-identical sibling and were followed up for at least a year. Pre-transplant preparation consisted of high-dose chemotherapy and/or radiation and post-transplant immune suppression consisted of methotrexate or cyclosporin-A. Data for 76 patients transplanted in first transplanted in either second to fourth remission, partial remission, or relapse. The 2-year actuarial survival-rate was 48% (95% CI, 36-60%) for patients transplanted in first remission and 30% 95% CI, 17-43%) for patients with more advanced disease (p = 0.037). Disease status at the time of transplantation was related to the probability of survival (p less than 0.02). The 2-year actuarial leukaemia recurrence-rate was 32% for patients transplanted in first remission and 50% for patients with more advanced disease (p = 0.0017). The probability of remaining in remission also was associated with disease status at time of transplantation (p less than 0.01). The incidence of graft-vs-host disease and interstitial pneumonitis was similar for patients transplanted in first remission and those transplanted later, and methotrexate and cyclosporin A were equally effective in modifying acute GVHD. These data indicate that prolonged survival can be achieved in approximately one-half of patients with acute myelogenous leukaemia given transplants of bone marrow from an HLA-identical sibling during their first complete remission.

BONE-MARROW TRANSPLANTATION IN HIGH-RISK ACUTE LYMPHOBLASTIC LEUKAEMIA IN FIRST AND SECOND REMISSION

Bone-marrow transplantation has been used in patients with acute lymphoblastic leukaemia (ALL) thought to be at high risk of relapse if managed with chemotherapy. Data from 444 ALL patients with one or more high-risk features at diagnosis were analysed to evaluate outcome after HLA-identical bone-marrow transplantation during first or during second remission. The 4-year actuarial probability of leukaemia-free survival was 45% (95% confidence interval 36-54%) for transplants in first remission compared with 22% (15-29%) for those in second remission (p less than 0.0002). The 4-year probabilities of relapse were 26% (14-38%) and 56% (45-67%) respectively (p less than 0.0001). For high-risk ALL, transplantation in first remission had clearly superior results to transplantation in second remission. Further studies are needed to determine whether patients with high-risk ALL should receive transplants during first remission or should initially receive chemotherapy, with transplantation being reserved for patients who relapse.

HLA C ASSOCIATIONS WITH ACUTE LEUKAEMIA

Frequencies of HLA A, B, C, and DR antigens were calculated in 1009 leukaemia patients, all of whom had been treated with bone-marrow transplantation and reported to the International Bone Marrow Transplant Registry. Cw3 (relative risk = 2 X 26, p = 0 X 00002) and Cw4 (relative risk = 2 X 18, p = 0 X 00003) were significantly associated with acute leukaemia (p values adjusted for multiple comparisons). Cw3 (relative risk = 2 X 97, p = 0 X 00002) and Cw4 (relative risk = 2 X 10, p = 0 X 004) were also significantly associated with acute lymphoblastic leukaemia and Cw4 was significantly associated with acute myelogenous leukaemia (relative risk = 2 X 39, p = 0 X 0003). The data suggest that Cw3 and Cw4 may be markers for leukaemia susceptibility genes, genes that code for low immune responsiveness to putative leukaemia viruses, or genes that regulate the response to chemotherapy and, therefore, the attainment of remission, since most of these patients underwent transplantation during remission.

BONE-MARROW TRANSPLANTATION FOR ACUTE LYMPHOBLASTIC LEUKAEMIA

106 patients with acute lymphoblastic leukaemia (ALL) who received bone-marrow transplants from HLA-identical siblings during first or second remission had an actuarial survival rate at 4 years of 43 +/- 12% and an actuarial relapse rate of 32 +/- 12%. 98 patients with more advanced disease had a significantly lower probability of survival (15 +/- 9%) and a significantly higher probability of relapse (67 +/- 14%). Among high-risk patients, those transplanted in first remission had a higher survival probability (55 +/- 22%) than those transplanted in second remission (41 +/- 15%). Relapse rates in the two groups were comparable (28 +/- 24% and 31 +/- 19% respectively). Standard-risk and high-risk patients transplanted in second remission had comparable relapse rates, but there was a trend towards higher survival probability in standard-risk patients. Thus long-term disease-free survival in ALL can be achieved with bone-marrow transplantation. It is not yet certain whether transplants in first remission will result in higher survival rates than transplants in second remission; relapse rates were similar in the two groups.

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.