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Thirty patients with chronic granulocytic leukemia (CGL), were given cyclophosphamide 60 mg/kg on each of 2 consecutive days, followed by total body irradiation (TBI) 10 Gy and an HLA-identical bone marrow transplant (BMT). Eleven patients were in the accelerated phase of their disease (CGLacc) or in second/secondary chronic phase (CGL-2CP), with a median age of 33 years: four patients died of transplant related complications, and four of recurrent leukemia; three patients are alive and well 19, 31, 33 months from BMT. The actuarial 33-month survival is 27%. The actuarial relapse rate is 50%. Nineteen patients were in their first chronic phase (1CP), with a median age of 32 years: three died of graft versus host disease (GvHD), two of infection, and two of acute respiratory distress syndrome (ARDS); 12 are alive and well 6 to 29 months post-BMT. The actuarial 29-month survival is 63%. The actuarial survival of patients younger than 30 years is 63%, compared to 62% for patients older than 30 (P = 0.1). The survival of patients grafted within or after 24 months from the onset of CGL is respectively 87% and 45% (P = 0.04). None of the patients grafted in 1CP had a true hematologic-cytogenetic relapse. The Ph' chromosome was detected on one occasion in two patients 12, 13 months post-BMT: they both remain hematologically normal and Ph1-negative 3 to 6 months later, after discontinuation of cyclosporin A. This study confirms that survival exceeding 60% can be obtained in CGL in the first chronic phase, whereas less than 30% of patients will survive if grafted in accelerated, second/secondary chronic phase, mainly because of leukemic relapse. The duration of the disease seems to be relevant to the outcome of the transplant. The effect of post-transplant immunosuppression, in our case cyclosporin A, on the interaction between normal and Ph1-positive hemopoietic cells, may deserve further attention.

A 28-year-old woman with Bence-Jones multiple myeloma (MM) presented with several osteolytic lesions and a massive bone marrow infiltration with mature plasmocytes. After 6 cycles of chemotherapy with melphalan and prednisone, the patient, in apparent clinical remission, underwent allogeneic bone marrow transplantation (BMT) from her brother. The patient has been followed up for 23 months, showing complete remission by clinical and laboratory criteria. Other cases of MM treated with BMT and reported in the literature are reviewed and discussed.

20 patients with acute nonlymphoid leukemia (ANLL) in first remission were given cyclophosphamide, 120 mg/kg, followed by total body irradiation (TBI) and an HLA-identical allogeneic marrow transplant (BMT). TBI was delivered in a single dose (10 Gy on day -1) in 2 patients, or in fractionated doses (3.3 rad/day on days -3, -2, -1) in 18 patients. The median age of patients was 22 years (range 2-44). Median time from remission to BMT was 5 months (range 1-12). 5 patients died of transplant-related toxicity (graft-versus-host disease with or without interstitial pneumonia) and 15 are alive 7-77 months post-BMT (median 20). The actuarial 72 months survival is 73%. There has been one relapse in a 2-year-old child, 4 months post-BMT, in the marrow and in the testis. The 72-month actuarial disease-free survival is 68%. The actuarial probability of relapse is 7%. This study indicates that a high proportion of ANLL patients treated in first remission with fractionated TBI and allogeneic marrow transplantation can become long-term disease-free survivors.

The authors report a case of hypertriglyceridemia complicating the course of a patient receiving cyclosporin A after bone marrow transplantation. When the patient was seen at the hemapheresis unit the clinical picture was characterized by headache, increasing visual and neurological disturbances. Plasma triglyceride level was 3215 mg/dl. Two plasma exchange sessions reduced triglycerides to 486 mg/dl and halted the disease progression. This may represent the first plasma exchange treatment of cyclosporin A-induced hypertriglyceridemia.

Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA-identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling.

If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n = 32) or leukemia (n = 142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P = 0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P = 0.06), older recipient's age (P = 0.08), fast engraftment (P = 0.03), and older donor's age (0.08) were also associated with a higher risk of GVHD. Recipient's ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P = 0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P = 0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.

This is a retrospective analysis of marrow function in 171 recipients of an HLA-matched bone marrow transplant (BMT). Only patients with detectable hemopoiesis as indicated by leukocyte counts greater than 1.0 x 10(9)/l and platelet counts greater than 25 x 10(9)/l who were alive on day 30 were entered in the study. Poor marrow function was detected in 24 (14%) patients as indicated by a decrease in the peripheral blood counts to less than 40% of the maximal preceding values post-transplant in association with reduced marrow cellularity. Leukopenia (n = 4), thrombocytopenia (n = 3) or a combination of the two (n = 17) occurred 62 +/- 23 (SEM) days post-transplant and was associated with acute graft-versus-host disease (AGVHD) grade II or more and infection (n = 19) in the absence of clear rejection or persistence/recurrence of malignant disease. A multivariate analysis showed that AGVHD was the major risk factor (p = 0.001) for developing poor graft function. In the 24 patients with poor graft function, hemopoietic recovery was strongly associated with resolution of AGVHD and of infections. Their survival (27%) was the same as survival for other patients matched for GVHD who had no pancytopenia. The causes of death were GVHD (n = 13), pneumonia (n = 3) and infections (n = 1). This study draws attention to a particular type of poor graft function following allogeneic BMT that is characterized by (1) normal timing and quality of engraftment, (2) AGVHD of grade II or greater, (3) progressive and severe pancytopenia, and (4) multiple infections with poor clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)