[ effectiveness of non-myeloablative stem cell transplantation and DLI as a selective treatment in class III beta-thalassemic patients]

At present, the only curative treatment for beta-thalassemia major is allogenic bone marrow transplantation accompanied with considerable mortality and morbidity in class III beta-thalassemia. Regarding few case reports on successful non-myeloablative stem cell transplantation in class III beta-thalassemic cases, we evaluated the effectiveness of this type of allogenic stem cell transplantation, considering less toxic non-myeloablative conditioning regimen. In this prospective study in Shariati Hospital bone marrow transplantation center during 2001-3, 13 class III beta-thalassemia patients [on the basis of history and physical examination and liver biopsy] were transplanted with peripheral blood and bone marrow stem cells from their HLA-identical siblings. Non-myeloablative conditioning regimen included fludarabine; busulan; antithymocyte globulin. Graft versus host disease [GVHD] prophylactic regimen was cyclosporin and metothrexate. In the case of the declining chimerism, the patients were treated with donor lymphocyte infusions [DLI]. The conditioning regimen was tolerated well without any considerable toxicity in hematologic, gastrointestinal and pulmonary systems. Five [38.5%] patients had acute and 2[15.4%] had chronic GVHD. Two patients died after transplantation. While two cases had a thalassemia-free survival. Although associated with high graft failure and the recurrence of disease, nonmyeloablative stem cell transplantation may be used as a curative, less toxic posttransplantation treatment for class III beta-thalassemia

Results of hematopoietic cell transplantation in pediatric leukemia

Hematopoietic cell transplantation [HCT] is an accepted treatment for acute myeloid leukemia [AML] in first remission, the treatment of choice for chronic myeloid leukemia [CML] and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings [57.6%] and autologous transplantation [42.4%]. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 +/- 4.7 X 10[8] /Kg [body weight of patients] and mononuclear cells were 5.5 +/- 2.9 X 10[8]/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin +/- methotrexate. GVHD occurred in 50 [54.3%] patients. Eighty five of children had engraftment, 26 [28.6%] relapsed and 57 [62%] are alive. The most common cause of death was relapse [68.6%]. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time [P = 0.06]. Longer survival significantly related to earlier WBC and platelet recovery [P < 0.0001 and P = 0.006 respectively]. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children

Effects of chimerism on graft versus host disease recurrence and survival after HLA identical marrow transplantation in Iran

The co-existence of recipient's hamatopoietic systems after allogeneic marrow transplantation is called mixed chimerism. Chimerism analysis provides a national method of different conditioning regimens, graft-versus-host disease [GVHD], prophylactic regimens, and cellular therapy to promote engraftment. The association of mixed chimerism with acute graft-versus-host disease [GVHD], disease recurrence, survival, and relapse free survival was investigated in 91 patients 12 and 79 of whom underwent either bone or peripheral blood HLA-identical marrow transplantation respectively. Chimerism was assessed using multiplex amplification of shorty tandem repeats [STR-PCR].cases included thalassemics [19 subjects], AML [29], ALL [20], CMT [18] and others [5].Median age was 21 [age range of 3-50]. There were 38 females [41.8%] and 53 males [58.2%]. Conditioning was busulfan plus cyclophosphamide in 34 patients, busulfan plus fludarabin in 51 patients and busulfan plus fludarabin plus anti-thymocyte globulin in 6 patients. Median of follow up was 13 months. Data was analyzed using SPSS statistical software. On day 30 after transplantation, mixed chimerism [MC] was observed in 15 patients [16.5%], complete donor chimerism [CC] in 72 patients [79%], and no chimerism in 4 patients. The incidence of acute GVHD was significantly lower in mixed chimeras that in complete chimeras [p=0.01] but there was no significant difference in acute GVHD grade [I, II vs. III, IV] between two groups. The incidence of relapse and overall survival were 17.6% and 88.9% respectively showing no significant difference between MC and CC. Relapse free survival was 80.2% and significantly different between two groups. Despite some previous reports, we found no significant difference in survival and relapse rate between MC and CC. Relapse free survival was 80.2% and not significantly different between tw ogroup

Frequency of BCR-ABL fusion transcript in Iranian patients with chronic myeloid leukemia

Reverse transcriptase-polymerase chain reaction [RT-PCR] assay is a useful tool for the detection of fusion transcript resulting from specific chromosomal translocation of the leukemia cells. A specific chromosomal abnormality, the Philadelphia chromosome [Ph], is present in 90% to 95% of CML patients. The aberration results from a reciprocal translocation between chromosome 9 and 22, creating a BCR-ABL fusion gene. There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 pro-tein. Another, less common fusion genes are b3a3 or b2a3 [p203] and e19a2 [p230]. The incidence of one or other rearrangement in chronic myeloid leukemia [CML] patients varies in different reported series. In general, fusion transcripts are determined individually, a process which is labor intensive in or-der to detect all major fusion transcripts. This study was designed to determine the frequency of different fusion genes in 75 iranian patients with CML. peripheral blood samples were analyzed by multiplex reverse transcriptase poly-merase chain reaction [RT-PCR] from adult patients to detect all types of BCR-ABL transcripts of the t [9:22] and found that all cases were positive for some type of BCR/ABL rearrangement. Most of our patients showed b3a2 fusion gene [62%], while the remaining showed one of the transcripts of b2a2, b3a3, b2a3, e1a2 or coexpression of b3a2 and b2a2. The rate of coexpression of the b3a2 and b2a2 was 5%. In contrast to the other reports, we did not see any coexpression of p210/p190. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences be-tween the populations studied. Coexpression may be due to alternative splicing or to phenotypic varia-tion, with clinical course different from classical CML