This study was undertaken to evaluate the occurrence of VOD and other liver diseases following BMT in a patient population with a high incidence of hepatitis before conditioning regimen. We prospectively reviewed 186 consecutive patients undergoing BMT from 1976 to 1986 to determine incidence and type of liver disease after BMT and predisposing factors. Two of 186 patients experienced VOD (1.07%). Acute and chronic liver GVHD were found in 25.8% and 36% of the patients, respectively. Acute hepatitis (AH) was diagnosed in 29.4% and chronic hepatitis (CH) in 42.6% of the patients. Statistical analysis showed no influence of pre-transplant variables on the occurrence of acute GVHD and AH; there was a weak correlation (P=0.01) between pre-BMT abnormal transaminases and occurrence of chronic GVHD. Contingency table and Cox analysis showed a greater risk of CH for patients with abnormal pretransplant SGPT levels (P=0.0004 and P=0.0022). No other variables could be associated with posttransplant CH. Actuarial survival was 71% versus 69% for patients with normal versus abnormal transaminases (P = 0.2). As VOD was a rare event, despite 53% of patients having abnormal transaminase values before transplant, we suggest that a lower and slower TBI is more important than pretransplant normal transaminases in preventing this complication. We conclude that evidence of compensated hepatitis is not a relative contraindication for BMT.
S ummary Bone marrow (BM) cells from 10 patients with Ph 1 ‐positive chronic granulocytic leukaemia (CGL) were placed in long‐term cultures in the presence of fetal calf serum (FCS) and horse serum (HoS), or in the presence of human AB serum. The long‐term cultures were started with three different cell combinations: (1) CGL BM cells (four cases), (2) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex‐matched sibling (five cases), (3) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex mismatched sibling (five cases). Cytogenetic studies were performed at weeks 0, 3, 4 and 5 of culture. The results of this study can be summarized as follows: (a) Ph 1 ‐positive cells could be detected at any time of culture in all three of the described cell combinations; (b) a population of Ph 1 ‐negative cells of patient origin could be detected after 3–5 weeks of culture; (c) there was a trend for a better survival of Ph 1 ‐negative cells in cultures supplemented with FCS + HoS and, conversely, of Ph 1 ‐positive cells in cultures containing human serum. These results warrant further studies on the possibility of manipulating survival and proliferation of normal and leukaemic cells by varying the culture conditions.
The prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3-7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
Twenty-seven patients with chronic myelogenous leukemia (CML)—17 in the chronic phase and 10 in the accelerated phase—were treated with an intensive chemotherapy regimen consisting of idarubicin, arabinosylcytosine, and etoposide. All patients were ineligible for bone marrow transplantation (BMT) and showed little or no cytogenetic response to interferon alpha (IFN-α). Blood hemopoietic cells (BHC) were collected by leukapheresis in all patients during early recovery from chemotherapy-induced aplasia. In 13/27 patients (48%), all metaphases were Ph-negative (Ph−); in another five patients, the percentage of Ph-positive (Ph+) metaphases decreased to less than 50%. Complete Ph+ disappearance was found in 66% of the patients treated within two years of diagnosis and in only 30% of those treated later. The collected Ph− cells have been used as autotransplants in nine patients: seven have shown sustained engraftment, and five are alive and well, with Ph− at 3+, 4+, 7+, 11+, and 19+ months after transplant It is remarkable that one patient, now Ph− at 19 months after transplant, is also PCR negative. These results suggest that it is possible to collect Ph− hemopoietic cells even years after diagnosis and to perform autologous transplants with these cells.
