Journal of Hematology - Supplements - Haematologica

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4 sources of hematopoietic stem cells include unrelated donors and autologous marrow. The results of BMT from unrelated donors demonstrate a 35% of DFS at 8 years. The search for an unrelated donor can be very long, so, when a related donor is not available, allogeneic BMT should be considered just as if chromosome alterations are present or in patients who do not respond to chemotherapy. Otherwise, transplants involving unrelated donors for AML in remission should proceed largely in the context of a clinical research protocol. 13 As far as regards autologous BMT, studies by both the Children Cancer Group and the Pediatric Oncology Group have not shown any difference in DFS between children receiving autologous transplant and those receiving continued chemotherapy (50% and 44%, respectively for the CCG study; 38% and 36% for the POG study). 12,13 Allogeneic bone marrow transplantation in chronic myelogenous leukemia Allogeneic or syngenic BMT is an effective treatment for chronic myelogenous leukemia (CML); 17 the results are dependent on the phase of the disease at the time of BMT. Allogeneic grafting should ideally be performed during the chronic phase within 1 year from diagnosis, but patients in advanced phases may also be treated with this procedure on an individual basis. Children who receive a transplant during blast crisis have a 10% to 20% DFS, those in accelerated phase have a 35% to 40% DFS, and those in chronic phase have a 50 to 80% DFS. Among chronic phase patients the major factor predicting outcome is the length of time between diagnosis and transplant: 17-18 those who receive a transplant within the first year after diagnosis have a DFS of 80-85% in the first 3 years, whereas those who receive a transplant more than 2 years after diagnosis have a DFS of 50-60%. 19 Unrelated donor marrow transplants give results similar to those obtained from suitably matched family member donors but are usually performed in the context of clinical research protocols. Allogeneic bone marrow transplantation in myelodysplastic syndromes Myelodysplastic syndromes (MDS) (Table 4) represent a heterogeneous group of clonal alterations of hematopoiesis, having in common cytopenia, dysplasia and a predisposition to evolve in acute myeloid leukemia (20-30% of cases). These disorders are typical of adult age: they represent only 2-9% of childhood hematologic malignancies; furthermore MDS of childhood appear to run a more aggressive course, Table 4. Myelodysplastic syndromes in children. PRIMARY MYELODYSPLASIA Refractory anemia (RA) Refractory anemia with ring sideroblasts (RARS) Refractory anemia with excess of blasts (RAEB) Refractory anemia with excess of blasts in transformation (RAEB/T) Juvenile chronic myeloid leukemia Congenital myelodysplastic sindrome SECONDARY MYELODYSPLASIA Familial Therapy induced Table 5. Constitutional abnormalities and somatic derangements associated with MDS in children. • Down’s syndrome • Trisomy chromosome 8 • Monosomy chromosome 7 • Ataxia-teleangectasia • Bloom’s syndrome • Xeroderma pigmentosus • Nijmegen’s syndrome • Neurofibromatosis I • Schwachman’s syndrome especially forms with elevated numbers of blasts in marrow (primary MDS). 15,20,21 Several conditions have been identified as predisposing factors for childhood MDS and are reported in Table 5. Refractory anemia, refractory anemia with ring sideroblasts and refractory anemia with excess of blasts in transformation Refractory anemia (RA) is frequent in children with familial hematologic disorders or constitutional problems. Refractory anemia with ring sideroblasts (RARS) is the least common of all the group: typically it is observed in girls with constitutional abnormalities and karyotype alterations (frequently monosomy 7); it can be a genetic mitochondrial disorder with polyclonal hematopoiesis that seldom progresses to leukemia but rather terminates in multiorgan failure; few cases of spontaneous regressions are described. Refractory anemia with excess of blasts (RAEB) and particularly with excess of blasts in transformation (RAEB/T) can be observed in older children: these forms are more aggressive than other myelodysplasias because of a higher progression rate to AML and poor survival. Allogeneic BMT performed early in the course of the disease and from the most closely matched source available confers the best hope for long-term survival. Some series record a dis- haematologica vol. 85(supplement to n. 11):November 2000
5 ease-free survival for childhood MDS as high as 60% following allogeneic transplantation. Patients transplanted for RA, RARS, RAEB, RAEB/T have a 5-year DFS of 52%, 34%, 19 % and 26%, respectively. The 5-year overall survival (OS) for the respective patient groups was 57%, 42%, 24% and 28%. In a multivariate analysis, younger age, shorter disease duration and absence of excess of blasts were associated with improved outcome. 20 Down’s syndrome was the most common affinity reported and one which is significantly associated with RAEB. As far AML, so far MDS in children with Down’s syndrome (or other constitutional alterations), the outcome is unfavorable. Moreover BMT for this group of patients appears to be associated with early mortality and to offer no advantages over conventional chemotherapy or supportive management. 16,18 Juvenile monocytic myeloid leukemia or juvenile chronic myeloid leukemia Juvenile chronic myeloid leukemia (JMML) is typical of very young patients (median 2.6 years old): it is characterized by prominent hepatosplenomegaly, frequent skin involvement, leukocytosis, monocytosis and presence of immature precursors in the peripheral blood. It is frequently associated with neurofibromatosis. 1 About 65% of patients with JCML have a normal karyotype, while 25% have monosomy 7 and 10% a complex of abnormal alterations. 19-22 Some young children with monosomy 7 karyotype share many of the clinical, laboratory and pathological features of JMML. Several study groups have attempted to classify this group of young children into a separate disorder called monosomy 7 syndrome. These patients did initially appear to differ from others with JMML because of a lower fetal hemoglobin level, and longer survival but higher rate of transformation to AML. However, more recent studies suggest that there are no data to support the concept of monosomy 7 as a truly separate disorder, but rather that it should be considered as a cytogenetic opportunist. 22 In a large series of patients with JMML the median survival without bone marrow transplantation was 1 year. Prognostic factors for duration of survival without BMT are platelet count at the time of diagnosis, age and HbF: 70% of patients aged < 2 years; platelets > 33,000/mL and HbF < 15% are still alive 3 years after diagnosis. Allogeneic BMT is the only therapy that has thus far produced unequivocal sustained remissions. The major limiting factor is an inordinately high percentage of relapse; allograft procedures can offer a 43% of 5-year survival. 19,21,22 Allogeneic bone marrow transplantation in severe aplastic anemia Aplastic anemia (AA) is a physiologic and anatomic failure of bone marrow’s with a marked decrease or absence of blood forming elements. It is characterized by peripheral pancytopenia without hepatomegaly, splenomegaly or lymphoadenopathy. The clinical presentation is related to the severity of the pancytopenia. The overall incidence is 2 to 4 cases per million children
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Page 5: 3 Table 1. Indications for allogene
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haematologica 2000; 85(supplement t
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