Bone marrow transplantation in adult thalassemia.

Early trials of allogeneic marrow transplantation for homozygous thalassemia were disappointing in patients older than 16, with four of six patients dying early of graft-versus-host disease-related complications, one patient dying at 9 months of infection due to graft failure, and one dying at 6 years of recurrent thalassemia. Three classes of risk could be identified in analyses of results of transplantation in younger patients using the criteria of degree of hepatomegaly, the presence or absence of portal fibrosis, and a history of adequate or inadequate chelation therapy. Patients for whom all three criteria were adverse constituted a very high risk group (class 3) for marrow transplantation. On the basis of these analyses, a conditioning regimen was designed that yielded superior results for class 3 patients under 17 years of age. Most patients older than 16 years presenting for transplantation have disease characteristics that place them in class 3 and, because of the improved results with the new class 3 regimen in younger patients, a study was designed to treat patients older than 16 years using treatment regimens assigned on the basis of disease class. Twenty patients were treated using this protocol and, with a minimum follow-up of 9 months, there have been three early deaths, one patient has recurrent thalassemia, and 16 patients are alive disease-free. The actuarial probabilities of survival, disease-free survival, and rejection are 0.85, 0.80, and 0.05, respectively, with a survival plateau extending from 6 months to 3 years. Marrow transplantation is a reasonable option for adults with progressive thalassemia who have suitable donors.

Sudden cardiac tamponade after chemotherapy for marrow transplantation in thalassaemia.

Published work suggests that cardiac tamponade occurs only occasionally after bone-marrow transplantation (BMT) but the worrying number of cases encountered in the transplant programme in Pesaro, Italy, has led to an analysis of this complication. Cardiac tamponade occurred in 8 (2%) of 400 consecutive thalassaemic patients during conditioning for or within a month of BMT. 6 cases were fatal; these represented 9% of all causes of death and 29% of those occurring between start of conditioning regimen and 30 days post transplant. The syndrome was characterised by sudden onset of circulatory shock and cardiac arrest. The only effective treatment was immediate fluid removal. The absence of myocardial lesions and the complete resolution of the syndrome after pericardiocentesis suggest that the pericardial membranes played the main part in the pathogenesis of the syndrome. Since irradiation was not part of the conditioning regimen and since 3 of the affected patients had bacteraemia, the triggering factor for the syndrome could have been the drugs used for conditioning, acting alone or together with bacteraemia and trauma. The frequency with which we encountered the syndrome, and the similarity among our patients in clinical picture, and in characteristics of the effusion, indicate that cardiac tamponade occurring in thalassaemic patients after start of chemotherapy as conditioning for BMT is a specific syndrome requiring rapid treatment.

Urothelial toxicity following conditioning therapy in bone marrow transplantation and bladder cancer: morphologic and morphometric comparison by exfoliative urinary cytology.

Since cyclophosphamide and busulphan used for therapy of bone marrow transplantation (BMT) can cause urothelial cell changes similar to those found in bladder cancer, comparative morphologic and morphometric urinary cytologic research was carried out, examining 812 urine samples taken from 121 patients undergoing BMT and 60 urine samples from 20 patients with bladder cancer. The morphological results showed some differences in the characteristics of the urinary sediment in urothelial toxicity caused by conditioning therapy in BMT and in bladder cancer; among these were background, cellularity, leukocytes, urothelial cell arrangement, cell shape and size, vacuolization, mitosis, and nucleoli. A comparative morphometric study was also carried out, showing differences regarding cell area, nuclear area and perimeter, and N/C ratio, especially between well-differentiated bladder cancer and urothelial toxicity.

Bone marrow transplantation in thalassemia.

Since 1983, 350 patients aged 1 to 19 years with beta-homozygous thalassemia were given infusions of HLA-identical marrow after high doses of busulphan and cyclophosphamide. Survival and event-free survival leveled off about 1 year after bone marrow transplantation at 82% and 75%, respectively. In 172 consecutive patients who were treated with our current regimen since June 1985, a multivariate analysis demonstrated that portal fibrosis, hepatomegaly, and a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly, portal fibrosis, and inadequate chelation therapy. Class 1 had none of the factors and class 3 had all three factors; class 2 had different associations of two out of the three factors. For class 1 patients, the 3-year probabilities of survival and event-free survival were 97% and 94%, respectively. For class 2 patients, the probabilities were 86% and 83%, and for class 3 patients, 58% and 52%. Bone marrow transplantation from HLA-identical donors is followed by a high probability of event-free survival in thalassemic patients, particularly if they belong to class 1.

Bone marrow transplantation in an HIV positive thalassemic child following therapy with azidothymidine.

The authors report their experience on allogeneic bone marrow transplant in an HIV seropositive thalassemic child. Before transplant a treatment with Azidothymidine was performed with the aim of reducing the viral load. Engraftment took place but, later, an explosive upsurge of viral disease occurred with encephalitis, positivation of the P24 antigen, proliferation of opportunistic infections and an increase of the IgG level. Furthermore the failure of CD4+ cell recovery was also observed. This case underlines that bone marrow transplantation can have a successful engraftment in HIV seropositive patients, but this doesn't modify the course of the infection.

Cytomegalovirus infections in thalassemic patients after bone marrow transplantation.

We report the incidence of cytomegalovirus (CMV) seroconversion, infections and mortality in 169 consecutive thalassemic patients transplanted in Pesaro. We observed a 44% incidence of early seroconversion and a 52% incidence of late seroconversion. No relationship was found between seroconversion and acute or chronic graft-versus-host disease (GVHD) or rejection. The donor status did not influence the incidence of seroconversion, GVHD and rejection. Only three patients died of CMV infection (1.7%); in each case CMV disease was the final cause of death in patients with severe acute GVHD.

Bone marrow transplantation in patients with thalassemia.

We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.

Allogeneic bone marrow transplantation for hematological malignancies following therapy with high doses of busulphan and cyclophosphamide.

Thirty patients with malignant hematological disease underwent allogeneic bone marrow transplantation following Busulphan (Bu) and Cyclophosphamide (Cy). The diseases were chronic myelogenous leukemia, acute lymphoblastic and non lymphoblastic leukemia, myelofibrosis and multiple myeloma in complete remission and in relapse. A sustained disease-free survival (DFS) was achieved in 0/5 acute leukemia patients transplanted in relapse, in 5/7 acute leukemia patients transplanted in remission (600-1550 days) and in 6/9 CML patients transplanted in the chronic phase of the disease (500-950 days). A sustained DFS was also achieved in one 2nd BMT for relapsed CML. The data suggest that the Bu-Cy protocol combines high tumor ablative capability with toxicity comparable to previously described conditioning regimens for allogeneic BMT, particularly in diseases involving a great expansion of the bone marrow.

Marrow transplantation for children with acute leukemia: experience of Pesaro.

Thirty children aged 1-15 years with acute lymphoblastic leukemia and acute nonlymphoblastic leukemia were transplanted from HLA-matched donors using two different preparative regimens: 18 patients were prepared with cyclophosphamide and total body irradiation (TBI) while 12 patients received busulphan and cyclophosphamide. Fifteen patients survived 7 to 74 months after transplant. The association of busulphan and cyclophosphamide is a well-tolerated preparation for bone marrow transplant in children with eradicating and immunosuppressive efficacy comparable to that of the well-experienced TBI-cyclophosphamide association.