European Bone Marrow Transplant Research Articles

A EUROPEAN MULTICENTER STUDY OF CHRONIC GRAFT-VERSUS-HOST DISEASE

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.

Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging

We analyzed data from 263 patients with acute myelocytic leukemia (AML) autografted in first remission (CR) during the period from January, 1982 to January, 1987 at one of 34 centers in the European Bone Marrow Transplant Group. The median age of patients was 30 years (range, 1 to 65). The median interval between achieving CR and autografting was 5 months (range, 1 to 23). Of the 263 patients, 131 patients received cytoreductive regimens that included total body irradiation (TBI); the remainder received various combinations of cytotoxic drugs. Sixty-nine patients received autologous marrow purged in vitro with mafosfamide, and 194 received unpurged marrow. The median follow-up was 28 months (range, 12 to 97). For patients with standard risk AML in CR1 autografted after TBI (n = 107), the leukemia-free survival (LFS) was higher, and the probability of relapse was lower in recipients of purged than of unpurged marrow (63% versus 34%, P = .05 and 23% versus 55%, relative risk 0.34, P = .005, respectively). The superior results of purging were most obvious in patients autografted within 6 months of achieving CR (probability of relapse, 20% versus 61%, P = .01). Patients with longer intervals between CR and autografting had higher LFS and lower probability of relapse than those autografted early in CR (intervals greater than 9 months, 7 to 9 months, 4 to 7 months, and less than or equal to 3 months: LFS = 56%, 40%, 35%, 27%, P = .007, probability of relapse = 25%, 56%, 59%, 67%, P = .005; respectively). We conclude that marrow purging with mafosfamide may be valuable for patients autografted early in first CR.

Autologous Bone Marrow Transplantation for Acute Myelocytic Leukemia in First Remission: A European Survey of the Role of Marrow Purging

We analyzed data from 263 patients with acute myelocytic leukemia (AML) autografted in first remission (CR) during the period from January, 1982 to January, 1987 at one of 34 centers in the European Bone Marrow Transplant Group. The median age of patients was 30 years (range, 1 to 65). The median interval between achieving CR and autografting was 5 months (range, 1 to 23). Of the 263 patients, 131 patients received cytoreductive regimens that included total body irradiation (TBI); the remainder received various combinations of cytotoxic drugs. Sixty-nine patients received autologous marrow purged in vitro with mafosfamide, and 194 received unpurged marrow. The median follow-up was 28 months (range, 12 to 97). For patients with standard risk AML in CR1 autografted after TBI (n = 107), the leukemia-free survival (LFS) was higher, and the probability of relapse was lower in recipients of purged than of unpurged marrow (63% versus 34%, P = .05 and 23% versus 55%, relative risk 0.34, P = .005, respectively). The superior results of purging were most obvious in patients autografted within 6 months of achieving CR (probability of relapse, 20% versus 61%, P = .01). Patients with longer intervals between CR and autografting had higher LFS and lower probability of relapse than those autografted early in CR (intervals greater than 9 months, 7 to 9 months, 4 to 7 months, and less than or equal to 3 months: LFS = 56%, 40%, 35%, 27%, P = .007, probability of relapse = 25%, 56%, 59%, 67%, P = .005; respectively). We conclude that marrow purging with mafosfamide may be valuable for patients autografted early in first CR.

Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG)

This retrospective survey of the EBMT Leukaemia Working Party describes 78 patients with myelodysplasia (MDS) or secondary acute myelogenous leukaemia (sAML) who received an allogeneic bone marrow transplant (BMT). The status of underlying disease at the time of transplantation was prognostic for the 2-year disease-free survival. Thirty-four patients received intensive chemotherapy prior to the conditioning for BMT. The 2-year disease-free survival was 60% for the 16 patients transplanted in complete remission. The results were significantly less favourable for those with more advanced disease who only partially responded to prior intensive chemotherapy (2-year disease-free survival: 18%) while none of those who either relapsed or were resistant to chemotherapy survived BMT for 2 years. Forty-four patients had not received any prior intensive chemotherapy. The disease-free survival at 2 years after BMT was 58 +/- 19% when a patient was transplanted for refractory anaemia (RA(S], 74 +/- 14% for refractory anaemia with excess of blasts (RAEB), 50 +/- 16% for RAEB in transformation (RAEBt), and 18 +/- 11% for secondary AML. Allogeneic BMT can therefore be considered as curative treatment for patients with MDS. Patients with sAML who have a histocompatible donor should be given chemotherapy intensive enough to induce complete remission. If this is achieved these individuals have a prognosis comparable to those with de novo AML in first remission after BMT.

Late effects of total body irradiation in correlation with physical parameters

Clear and complete documentation of the physical parameters of total body irradiation (TBI) is one of the essential requirements for the evaluation and improvement of the clinical results of TBI. Concerning the dosimeric aspects of TBI, a number of recommendations have been formulated with emphasis on basic dosimetry, patient dosimetry and dose specification. The dosimeters should be calibrated regularly with reference to the absorbed dose in water. Depth dose measurements should be performed in water equivalent phantoms of specified dimensions. It has been strongly suggested to measure the absorbed dose at the surface of the patient at 8 different regions at the entry and exit of the beam under TBI conditions. The reference dose to the patient should be specified as the total dose to mid abdomen at the height of the umbilicus. As an independent parameter, the lung dose should be specified as the mean dose in the central region of the shielded part of both lungs. Recent, more complete, information on the physical and dosimery aspects of TBI will be incorporated in the registry of the European Bone Marrow Transplant Group (EBMT). A cooperation has been established between the EBMT and the European Late Effects Project Group (EULEP) to study the development of late effects in man caused by ionising radiation.

ALLOGENEIC BONE MARROW TRANSPLANTATION FOR LEUKAEMIA IN EUROPE: REPORT FROM THE WORKING PARTY ON LEUKAEMIA, EUROPEAN GROUP FOR BONE MARROW TRANSPLANTATION

1957 allogeneic HLA-identical sibling-donor bone-marrow transplants done in 52 European centres between 1979 and 1986 and reported to the European bone-marrow transplant leukaemia registry were analysed. The most important factor influencing leukaemia-free survival, transplant-related mortality, and relapse incidence was the stage of the disease at the time of the transplant. This dominant role of the stage of the disease in all three diagnostic categories—acute myeloblastic leukaemia, acute lymphoblastic leukaemia, and chronic myeloid leukaemia—for all three end-points clearly indicates that resistance of the leukaemia cell to the procedure is more important than bulk of the disease. Additional prognostic factors for leukaemia-free survival and transplant-related mortality were age of the patient, cyclosporin for preventing graft-versus-host disease, and the donor-recipient sex combination. The risk of relapse was highest in patients with acute lymphoblastic leukaemia. In a multivariate analysis leukaemia-free survival was similar for all three major diagnostic categories and has not changed since the introduction of the European registry in 1979. These results show that the biological differences between the three main diagnostic categories of leukaemia are not as great as had been assumed and that the traditional approaches to improving results in recent years have failed.