Journal of Hematology - Supplements - Haematologica

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6 patients grafted in Europe from 1976 to 1998 and demonstrated that factors predicting outcome of those patients are: age at time of graft, donor type, interval between diagnosis and BMT, year of BMT and female donor to male recipient. Patients were then divided into two groups according to the year of BMT: up to or after 1990. The overall death rate dropped from 43 to 24%. Improvements are seen mostly for grafts from identical siblings (from 54 to 75%) and less for alternative donors (from 28 to 35%). 26 Chronic GVHD is the major cause of death in long-term survivors of BMT. The relative risk of death is higher when BMT is performed more than 1 year after diagnosis, after acute GVHD or in the presence of active chronic GVHD 2 years after BMT. The actual survival rate is 85% in subjects without chronic GVHD and 69% in patients with GVHD. For this reason prophylaxis of GVHD is important: major changes are related to the increased use of cyclosporine with or without methotrexate. 27 The continuing mortality after treatment, especially when only immunosuppressive therapy is given, is largely attribuible to a high risk of developing clonal marrow disorders (3.1% in BMT recipients versus 18.8% in patients managend only with immunosuppressive therapy). This risk is higher in subjects with congenital AA (elevated percentage of genetic abnormalities). The risk of developing solid tumors is similar in patients treated with allogeneic BMT and in those treated with immunosuppressive therapy alone (2.2%). 27 Allogeneic bone marrow transplantation in thalassemia major BMT in thalassemia major was successfully accomplished in 1982. Much additional experience has been gained since. The improvements in results are related to better selection of the patients for BMT: patients with thalassemia major selected for allogeneic bone marrow transplant can be allocated to three classes with respect to the three following risk factors: entity of hepatomegaly, portal fibrosis on pre-transplant liver biopsy and chelating treatment before transplantion (Table 7). Each patient with an HLA-identical donor is assigned to a protocol of treatment exclusively on the basis of the class: the first two classes are treated with the same protocol (cyclophosphamide, busulfan and cyclosporine) with a survival rate and EFS of 87% and 84%, respectively. Class 3 patients are prepared for BMT with the same drugs but the doses are lower because of Table 7. Classes of risk for patients with thalassemia major selected for allogeneic BMT. Class 1: score 0 Class 2: score 1-2 Class 3: score 3 Iron chelation history: Score 0 = “regular”, i.e. by subcutaneous infusion for 8- 10 hours at least 5 days/week and started within 18 month from the 1st transfusion Score 1 = “irregular”, i.e. any deviation from the above Hepatomegaly: Score 0 = liver less than 2 cm below the costal margin Score 1 = liver enlarged 2 cm or more Portal fibrosis on pre-transplant liver biopsy: Score 0 = no fibrosis Score 1 = presence of fibrosis Table 8. The Pesaro experience. Class N° of risk Long-term Disease-free Rejection Mortality factors survival survival (>10 yr) 1 0 92% 85% --- 8% 2 1-2 84% 80% 5% 16% 3 3 61% 53% 16% 29% 317 yr 3 63% 60% 4% 39% the hepatic complication; the survival rate and EFS are 89% and 64% respectively. 28-30 Over 1,000 patients have now been transplanted in several highly experienced centers, the largest series being at Pesaro, Italy (Chief: G. Lucarelli). Table 8 summarizes the Pesaro experience of patient survival, disease-free survival and risk of GVHD in these three groups. 30 The long-term effects of BMT in thalassemia are being monitored in patients transplanted between 1987-1995 and compared with those subjects matched for age and treated during the same period with conventional therapy. The incidences of fulminant sepsis and growth impairment are significantly higher in transplanted patients, whereas the occurrence of hypothyroidism, hypogonadism, and cardiomyopathy are higher in the other group of patients. Non-significant differences are observed in the incidences of diabetes, liver disease, and severe infections. 29-32 After successful marrow transplantation, iron overload remains an important cause of morbidity in patients with thalassemia. Phlebotomy represents a safe, efficient and widely applicable method to decrease iron overload. One study demonstrates that moderately intensive phlebotomies can help to reduce iron overload and improve cardiac status. The same results can be obtained in the same time with desferroxamine. 33 haematologica vol. 85(supplement to n. 11):November 2000
7 Allogeneic bone marrow transplantation in sickle cell disease Hematopietic stem cells transplantations with bone marrow or umbilical cord blood from HLA-identical sibling donors have shown that sickle cell disease (SCD) can be cured with stabilization of prior organ damage. 34-36 In spite of this, very few patients with sickle cell anemia undergo an allograft procedure in comparison to β-thalassemic patients.This is probably due to the more variable clinical course of SCD and to the limitation of eligibility to those patients with advanced symptomatic disease (Table 9), often with neurologic and pulmonary vasculopathy. 34,35 Although most children grafted with HLAidentical marrow survive free of SCD, 34-36 several follow-up evaluations of patients with stable engraftment are required to assess the effective cessation of clinical vaso-occlusive events, the beneficial effect of donor erythropoiesis on SCD-related organ damage and possible late effects of the transplants related to the administration of myeloablative chemotherapy. Walters et al. studied 50 children transplanted with matched sibling marrow between 1991 and 1999: Kaplan-Meier probabilities of survival and event-free survival were, respectively, 94% and 84%. All patients were evaluated for late effects of BMT and for its impact on sickle-cell related central nervous system (CNS) and pulmonary disease. BMT established normal erythropiesis in most patients who had stable donor engraftment: complications related to SCD resolved, pulmonary function tests were stable and all patients with a prior history of stroke had stable or improved cerebral nuclear magnetic resonance imaging results. No patients had episodes of pain, stroke or acute chest syndrome. Linear growth improved. 34 However, an analysis of outcome of patients with a high risk of stroke events, treated with Table 9. Inclusion criteria for transplantation in patients with SCD. • Age of patient
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