Long-term results of non-fludarabine versus fludarabine-based stem cell transplantation without total body irradiation in Fanconi anemia patients

Hematopoietic cell transplantation [HCT] is the only therapeutic modality capable of correcting the hematologic manifestations of Fanconi anemia [FA]. The development of well-tolerated immunosuppressive conditioning regimens for FA patients undergoing HCT has proven to be a challenging task for hematologists. Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center. We analyzed the outcome of 53 FA patients who had undergone HCT between 1992 and 2010. The median age at transplantation was 9 years. Patients received transplants from an HLA-identiccal sibling [n=39] or matched relative [n=9] and one-antigen locus mismatched other relative/sibling [n=5]. All of the patients underwent transplantation with fludarabine and non-fludarabine-based conditioning regimens. No radiation therapy was given. The median follow-up period for survivors was 13.5 months [range, 3 months-13.5 years]. The 3-year overall survival [OS] was 60.6%. The 3-year OS for patients who did or did not receive fludarabine-based preparative regimens for the allograft was 36.4%, and 70%, respectively. However, there were no statistically significant differences in OS rates between these two groups [P=.112]. Graft failure occurred in 4 patients [7.5%]. All of these 4 patients had received fludarabine-based conditioning regimens. The incidence of acute GVHD after fludarabine-based regimens was 45% versus 79% in non-fludarabine-based regimens [P=.03]. Despite the high incidence of acute GVHD [78.6%] in the non-fludarabine group, which ressulted in the death of some patients, the OS rate was significantly better than in fludarabine recipients. Therefore, in spite of the fact that recent studies advocate the fludarabine-based conditioning regimens, we propose to conduct a multicenter, prospective study to evaluate the outcomes of regimens employed in FA patients

Hematopoietic stem cell transplantation in acute promyelocytic leukemia, experience in Iran

Acute promyelocytic leukemia is a rare indication for hematopoietic stem cell transplantation. Usually it is indicated as consolidation of salvage regimens following relpase. Here we report our experience with stem cell transplantation in acute promyelocytic leukemia patients. Between 1989 and 2011, we performed 40 hematopoietic stem cell transplantation in first complete remission or relapsed acute promyelocytic leukemia patients. Median age of patients was 23.5 years. Patients received 11 autologous and 29 allogeneic hematopoietic stem cell transplantation from their HLA fully-matched sibling donors. Different conditioning regimens were applied. A total of 24 patients received hematopoietic stem cell transplantation who were in first complete remission and the remainder with a second or more complete remission. Hematopoietic stem cell engraftment was observed in all cases. There were no deaths prior to 100 days after hematopoietic stem cell transplantation. Acute graft versus host disease was mild to moderate in the majority of patients, whereas it was grade III in 4 patients. Chronic graft versus host disease was extensive in 2 cases. With a 4-year median follow up, the relapse rate was 25%. A total of 26 patients are alive. Five year overall survival was 65.5% and 46.8% for allogeneic and autologous hematopoietic stem cell transplantation, respectively. Hematopoietic stem cell transplantation is an acceptable treatment for acute promyelocytic leukemia. Although there is a statistical difference for overall survival between allogeneic or autologous hematopoietic stem cell transplantation, the choice between autologous or allogeneic transplantation needs to have reliable methods for the detection of molecular remission before hematopoietic stem cell transplantation as well as close, reliable follow up of patients with clinical and molecular parameters

Frequency, risk factors, and outcome of acute kidney injury following bone marrow transplantation at dr shariati hospital in Tehran

Bone marrow transplantation [BMT] is a major modality for malignant and hematologic disorders. This procedure is associated with a high morbidity and mortality such as acute kidney injury [AKI]. Many factors, such as therapeutic agents, irradiation, and graft versus host disease [GVHD] can cause AKI. Bone marrow transplantation conditioning therapy in Iran is based on drugs such as busulfan and cyclophosphamide and without irradiation therapy. The aim of this study was to evaluate the frequency, risk factors, and mortality of AKI among patients who underwent BMT. Acute kidney injury was defined as doubling serum creatinine from baseline at any time during the first 180 days posttransplant. The risk of AKI in relation to non-total-body-irradiation-based conditioning regimen, type of graft [allograft and autograft], comorbidities, GVHD, drug toxicity, and veno-occlusive disease were examined in 375 patients with BMT. One hundred and forty-two patients [37.6%] developed AKI at a median of 18 days after transplant. A higher frequency of AKI was observed in patients who received cyclosporine A [40%], patients with allograft BMT [42.1%], and those who developed gastrointestinal GVHD [47.3%] .The remainder AKI cases were associated with amphotericin B, veno-occlusive disease, and hemolytic-uremic syndrome. The frequency of AKI in our patients with BMT remained high. Cyclosporine A and amphotericin B and the presence of GVHD and veno-occlusive disease increased the risk of AKI within the first 180 days after BMT

Low dose psoralen plus ultraviolet a [PUVA] is an effective and safe method for the treatment of chronic graft versus host disease

Chronic graft versus host disease [ch.GVHD] is the most frequent late complication after allogenic stem-cell transplantation. Systemic immunosuppressive agents are usually required to control the disease. Psoralen plus UVA [PUVA] has been used for the treatment of ch.GVHD with variable beneficial effects. The objective of this study was to assess the efficacy and safety of a relatively lower dose of oral psoralen compared with previous reports, for the treatment of ch.GVHD patients with PUVA. Eleven patients who received allogenic bone marrow transplantation and had severe progressive ch.GVHD that was unresponsive to conventional immunosuppressive treatments were treated with oral 8-methoxypsoralen [0.2 mg/kg, up to 10 mg] two hours before exposure to UVA. The patients received a median of 43 treatments [range: 18 to 72]. Mean cumulative dose of UVA was 200.5 J/cm2 [range, 116.5-306.5 J/cm2]. In four of the 11 patients, there was a complete resolution of cutaneous ch.GVHD and the remaining seven patients achieved partial response with PUVA treatment. Complete and partial remission was observed in four and six patients with lichenoid lesions, respectively, but all of the four patients with sclerodermoid GVHD showed partial response to PUVA treatment. We observed no side effects like phototoxicity, nausea and vomiting, and exacerbation of GVHD. Liver enzymes raised in five patients, causing no significant morbidity for them. Low-dose psoralen plus UVA can be a safe and effective therapy for chronic cutaneous GVHD. Although the number of treatments and total cumulative exposure to UVA was rather high in our study, we observed no phototoxic reaction or severe irreversible liver damage due to phototherapy, which may be because of a relatively lower dose of methoxsalen used in our patients. Psoralen plus UVA is effective particularly in lichenoid GVHD lesions but sclerodermoid lesions may also benefit from this therapy

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

A specific chromosomal abnormality, the Philadelphia chromosome, is present in 90 - 95% of patients with chronic myeloid leukemia. The aberration results from a reciprocal translocation of chromosomes 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 transcript b2a2 or b3a2 codes for a p210 protein. Other fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Other less common fusion genes are b3a3 or b2a3 [p203] and e19a2 [p230]. The incidence of one or other rearrangement in chronic myeloid leukemia patients varies in different reports. In general, fusion transcripts are determined individually, a process which is labor- intensive in order to detect all major fusion transcripts. The objective of this study was to set up a multiplex RT-PCR assay for detection and to determine the frequency of different fusion genes in 75 Iranian patients with chronic myeloid leukemia. Peripheral blood samples were analyzed by multiplex RT-PCR from 75 adult Iranian chronic myeloid leukemia patients to detect different types of BCR-ABL transcripts of the t[9;22]. All patients examined were positive for some type of BCR/ABL rearrangement. The majority of the patients [83%] expressed one of the p210BCR-ABL transcripts [b3a2, 62% and b2a2, 20%], while the remaining showed one of the transcripts of b3a3, b2a3, e1a2 or co-expression of b3a2 and b2a2. The rate of co-expression of the b3a2 and b2a2 was 5%. In contrast to other reports, we did not see any co-expression of p210/p190. Co-expression may be due to alternative splicing or to phenotypic variation, with clinical course different from classic chronic myeloid leukemia

Hematopoietic stem cell transplantation in Iran: 1991 to 2008

Since 1991, 2042 first hematopoietic stem cell transplants [HSCT] have been performed at the Hematology-Oncology and Stem Cell Transplantation Research Center at Tehran University of Medical Sciences. Acute myelogenous leukemia [548 patients], thalassemia major [335 patients] and acute lymphoblastic leukemia [275 patients] have been the most common transplanted disorders. There were 1418 cases that received allogeneic HSCT and 624 cases that have received autologous HSCT. The numbers of allogeneic and autologous HSCT have increased, but the allogeneic to autologous ratio has remained constant. The first peripheral blood hematopoietic stem cell transplantation was performed in 1996; since then, 1671 have been done. The donor types for 1418 allogeneic first HSCT were 1367 [96.4%] human leukocyte antigen [HLA] matched-identical siblings, 29 [2%] HLA-mismatched sibling/other relative, 13 [0.9%] syngeneic twins, 5 [0.4%] HLA-matched other relatives and 4 [0.3%] unrelated. The first cord blood hematopoietic stem cell transplantation was performed in 1998 and since then there have been 14 patients that have obtained cord blood transplantations. Recently, new methods have been used like donor lymphocyte infusion [DLI] and cellular therapy. There were 111 patients with cellular therapy for post-myocardial infarction, cirrhosis, thalassemia major, multiple sclerosis, head of femur necrosis and renal cell carcinoma

Treatment of chronic cutaneous graft versus host disease [GVHD] with photochemotherapy with psoralen [PUVA]: a report of five cases

Chronic graft versus host disease [GVHD] remains the most common late complication of allogenic stem cell transplantation and the most frequent cause of morbidity and mortality in these patients. To control this condition, immunosuppresive drugs are usually administered at a high dose and for a long time, which may result in several side effects. Five patients with clinically and histopathologically established cGVHD [3 lichenoid, 1 sclerodermoid and 1 mixed lichenoid-sclerodermoid], who failed to respond to conventional immunosuppressive therapy were treated with psoralen and UVA [PUVA].Treatment was administered in a standard protocol three times a week on nonconsecutive days and were continued at least for 12 weeks. All 3 lichenoid cases showed complete improvement. In the sclerodermoid case there was partial response and in the mixed type case the partial response of sclerodermoid lesion and complete response of lichenoid lesions were observed. With the exception of a slight increase in liver tranferases, no other adverse reactions occurred. In conclusion, PUVA can be a safe and effective therapy in conjunction with systemic agents for chronic GVHD especially in lichenoid form