Publications by authors named "Babak Bahar"

24 Publications

  • Page 1 of 1

Long--Term Free Survival of Two Class III β-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation.

Int J Hematol Oncol Stem Cell Res 2020 Apr;14(2):118-122

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemia patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemia patients. Two successful Fludarabine-based non-myeloablative stem cell transplantation in two Class III β thalassemia patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation. After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemia patients, we concluded that Fludarabine-based non-myeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemia patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231797PMC
April 2020

Comparison of the Efficacy of Topical Triamcinolone in Orabase and Curcumin in Orabase in Oral Graft-Versus-Host Disease.

J Dent (Tehran) 2017 Nov;14(6):313-320

Postgraduate Student, Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Graft-versus-host disease (GVHD) is among the most frequent complications of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD has several clinical manifestations in the oral cavity, including painful desquamative erythema, ulcerative mucosal lesions, and lichenoid lesions. The patients presenting with oral GVHD complain of oral sensitivity, pain, dysgeusia, and xerostomia. The treatment of oral GVHD includes a proper systemic therapy combined with a good oral hygiene and the use of local and topical steroids. Corticosteroids and immunosuppressants are used for the treatment of chronic oral GVHD; however, they are associated with different complications. Evidence shows that curcumin has anti-inflammatory and antioxidative properties. The treatment of lichen planus and oral mucositis with curcumin has been successful. This study aimed to compare the efficacy of topical curcumin in Orabase and triamcinolone in Orabase in the patients affected by oral GVHD.

Materials And Methods: Twenty-six patients presenting with oral GVHD were randomly divided into two groups of 13 using block randomization. The control group used triamcinolone in Orabase, and the case group received curcumin in Orabase.

Results: The two groups were not significantly different in terms of the alleviated severity of the lesions at the end of the treatment (P=0.052). The comparison of the pain score via the visual analog scale (VAS) at the onset of the treatment and at days 14 and 28 (completion of the treatment) showed no significant difference between the two groups (P>0.05).

Conclusions: Curcumin has comparable efficacy to that of triamcinolone and may be prescribed for the patients presenting with oral GVHD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015590PMC
November 2017

Conjugated Estrogen in Late-Onset Hemorrhagic Cystitis Associated with Hematopoietic Stem Cell Transplantation.

Int J Hematol Oncol Stem Cell Res 2017 Jan;11(1):13-18

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Hemorrhagic cystitis (HC) is one of the most challenging complications in hematopoietic stem cell transplantation (HSCT). Estrogen is one of the suggested treatments for controlling this problem. We performed a randomized case-control study to evaluate the efficacy of oral conjugated estrogen on HC management in 56 HSCT patients. Patients were randomly assigned to the drug group (received 6.25 mg conjugated estrogen oral tablets in a daily single dose during hematuria period) or control group. The median time to complete response was 36 and 24 days in the drug and control group, respectively. The median time of down stage was 24 days in the drug group and 12 days in control group. Adjusted for HC grades, the relative risk of complete response for patients in control group was 1.613 times more than that of patients in drug group; nevertheless, not significant (p=0.122). Our study did not show any benefit in use of oral conjugated estrogen in the management of HC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338276PMC
January 2017

Nephrotic Syndrome After Hematopoietic Stem Cell Transplant: Outcomes in Iran.

Exp Clin Transplant 2017 Feb;15(Suppl 1):90-92

Nephrology and Transplant Ward, Hashemi Nejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran.

Objectives: Patients undergoing hematopoietic stem cell transplant have an elevated incidence of acute renal failure. However, the incidence of nephritic syndrome due to graft-versus-host disease is growing and is independently associated with chronic renal disease after this procedure.

Materials And Methods: We conducted a prospective study to examine the risk of chronic kidney disease in glomerulopathy patients following hematopoietic stem cell transplant with a follow-up of 10 years.

Results: In our follow-up of 14 patients (4 men and 10 women) who were diagnosed with nephrotic syndrome after hematopoietic stem cell transplant, in 10 patients (71%), biopsy showed membranous nephropathy associated with graft-versus-host disease. The remaining 4 patients had focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, or minimal change disease. All patients were treated with angiotensin receptor blockers, cyclosporine (Neoral), and prednisolone. During follow-up, 6 patients (43%) had heavy proteinuria and a rise in serum creatinine, and 1 patient (7%) needed hemodialysis. Eleven patients (79%) achieved complete remission of nephrotic syndrome, 5 (36%) remained hypertensive, and 3 (21%) did not respond to therapy..

Conclusions: The early diagnosis of nephrotic syndrome should be considered after hematopoietic stem cell transplant, and therapeutic outcome measures should be in place in advance. If this is done, we found that patients' response to treatment can be optimal, and their renal function and overall survival can improve.
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http://dx.doi.org/10.6002/ect.mesot2016.O70DOI Listing
February 2017

Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with Fanconi Anemia.

Mediterr J Hematol Infect Dis 2016 1;8(1):e2016054. Epub 2016 Nov 1.

Hematology, Oncology and Stem Cell Transplantation Research Center; Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Fanconi anemia (FA) is a rare genetic disorder caused by an impaired DNA repair mechanism which leads to an increased tendency toward malignancies and progressive bone marrow failure. The only curative management available for hematologic abnormalities in FA patients is hematopoietic stem cell transplantation (HSCT). This study aimed to report the results of HSCT in adult or adolescent FA patients.

Patients And Methods: Twenty FA patients with ages of 16 or more who underwent HSCT between 2002 and 2015 enrolled in this study. The stem cell source was peripheral blood, and all patients had a full human leukocyte antigen (HLA) matched donor, 19 patients had a sibling donor, and one had full matched other related. Indications for HSCT were severe bone marrow failure or dependence on blood products transfusion and failure of medical treatment to sustain peripheral blood elements at an acceptable level.

Results: Eleven patients were female and 9 male (55% and 45%). Mean age was 24.05 years. Mortality rate was 50% (n=10), and the leading cause of death was graft versus host disease (GVHD) which occurred in 5 patients (4 cases from acute GVHD and one from chronic GVHD). Survival analysis showed an overall 5-year survival of 53.63% (95% confidence interval: 29.53%-72.74%) and 13 year survival of 45.96 % (95% confidence interval: 22.08%-67.03%) among patients.

Conclusion: HSCT is the only curative management for bone marrow failure in FA patients. But the high rate of mortality and morbidity in adolescent and adult patients makes it a challenging issue.
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http://dx.doi.org/10.4084/MJHID.2016.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111526PMC
November 2016

Allogeneic hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: a retrospective single-center study.

Hematol Oncol 2017 Dec 20;35(4):935-938. Epub 2016 Oct 20.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cell characterized by complement mediated intravascular hemolysis. There are different treatment modalities available for PNH, such as supportive care, eculizumab, and hematopoietic stem cell transplantation (HSCT); only the last one has a potential curative role. This study reported the outcome of HSCT transplanted PNH patients. Thirteen PNH patients between 2002 and 2014 participated in this study. All had full-matched sibling donors, and the conditioning regimen was Bu/Cy (busulfan plus cyclophosphamide), and the source of stem cells was peripheral blood of the donors. Mean age at transplant was 27.46 years, and mean time to transplant was 41.30 months. Three were female and 10 were male. Three patients died at the end of follow-up time, and the cause of death was graft versus host disease (GVHD) for all 3 cases. Survival analysis showed a 5-year and a 13-year survival rate of 74.07% and a significant relationship between a positive history of thrombosis and a higher mortality rate. HSCT has curative role in management of PNH with an acceptable survival rate and therefore can be considered as an acceptable choice for selected cases.
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http://dx.doi.org/10.1002/hon.2367DOI Listing
December 2017

Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran.

Asian Pac J Cancer Prev 2016 ;17(2):603-8

Gastrointestinal and Liver Diseases Research Center, Firoozgar Hospital, Iran University Of Medical Sciences, Tehran, Iran E-mail :

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features.

Materials And Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these.

Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics.

Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.
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http://dx.doi.org/10.7314/apjcp.2016.17.2.603DOI Listing
January 2017

Chromogenic In Situ Hybridisation Test for Breast Cancer Patients with Equivocal IHC Results--a Study from Iran.

Asian Pac J Cancer Prev 2015 ;16(17):7695-700

Oncopathology Research Center and Department of Pathology, Iran University of Medical sciences, Tehran, Iran E-mail :

Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions.

Materials And Methods: This study was conducted from 2008- 2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results.

Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively.

Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.
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http://dx.doi.org/10.7314/apjcp.2015.16.17.7695DOI Listing
September 2016

Comparison of 60 and 80 mg/m of daunorubicin in induction therapy of acute myeloid leukaemia.

Hematol Oncol 2017 Mar 3;35(1):101-105. Epub 2015 Aug 3.

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

For finding better method of acute myeloid leukaemia (AML) induction, we designed a prospective clinical trial to find a more effective regimen with least toxicity for induction therapy of AML. Hence, we examined different accepted doses of daunorubicin and their outcomes. Total of 114 patients were included in the study. Fifty-five patients received 60 mg/m of daunorubicin (arm 1) 1 h IV infusion for 3 days, and the remaining 59 received 80 mg/m (arm 2) 1 h IV infusion for 3 days. Continuous infusion of 100 mg/m /day of cytosine arabinozide IV for 24 h for 7 days was given in both groups. Complete remission rate was 77.78% in group 1 and 76.92% in group 2 (p = 0.92). One-year overall survival was 55.85% [standard error (SE) = 8.05%] in arm 1 and 57.94% (SE = 7.32%) in arm 2. Median follow-up time was 11.1 (SE = 1.43) and 10.28 (SE = 1.29) months, respectively. One-year disease-free survival was 64.41% (SE = 7.39%) in arm 1 and 54.86% (SE = 7.53%) in arm 2. Complete remission, overall survival and disease-free survival were statistically the same in both groups (p = 0.92, 0.697, 0.31). Toxicity and safety profile were similar in two groups but need to transfusion was higher in arm 2. Febrile neutropenia, days of antibiotics consumption and invasive fungal infection prevalence did not show any difference. Mean transfused packed cells and platelets rate were higher in the group that received higher dose of daunorubicin. Considering these results, we found that 60 mg/m of daunorubicin would be more rational and as effective with lower toxicity to 80 mg/m in induction therapy of AML patients at least as scheduled in our trial. Copyright © 2015 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/hon.2236DOI Listing
March 2017

The EBMT Risk Score in the Presence of Graft Versus Host Disease in Allogeneic Stem Cell Transplantation in Adult Acute Myelogenous Leukemia: A Multistate Model for Competing Risks.

Int J Hematol Oncol Stem Cell Res 2014 Jul;8(3):1-11

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The aim of this study was to assess the predictive effect of the EBMT risk score on the outcomes of allogeneic stem cell transplantation in a relatively homogenous group of acute myelogenous leukemia (AML) patients regarding the occurrence of acute and chronic graft versus host disease (GVHD). This historical cohort study included adult patients (≥ 15 years old) with AML (n=363) who received allogeneic peripheral blood stem cell transplantation from HLA-identical sibling donors in the first or higher complete remission following myeloablative conditioning regimens between 2004 and 2011.The patients recruited in this study were followed-up until January 2013. Patients with acute promyelocytic leukemia (APL) were excluded from the study. Early outcomes until day +100 and events after day +100 were regarded for acute and chronic GVHD, respectively. A multi state model for competing risks was applied. We found that the EBMT risk score was a good predictor for overall survival (OS) and relapse incidence; however, it was not associated with transplant-related mortality (TRM). The EBMT risk score was not associated with acute and chronic GVHD. For early outcomes, the predictive effect of the EBMT risk score was not statistically significant in the presence of acute GVHD; however, in the presence of chronic GVHD, it was a significant predictor of relapse but not for TRM. It seems that the effect of EBMT risk score on OS and relapse incidence cannot be affected by GVHD. Although the results were insignificant, there was evidence that the EBMT risk score can predict early outcomes, while for late outcomes, it works well for relapse and OS but not for TRM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305375PMC
July 2014

The outcomes of esophageal and gastric cancer treatments in a retrospective study, single center experience.

Int J Hematol Oncol Stem Cell Res 2014 ;8(2):9-13

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Esophageal and gastric cancers are among the most common cancers in Iran. Usually survival of these cases is poor despite of treatment. Here we studied outcome of these cases in our center to have an estimation of general prognosis of patients.

Methods: In this retrospective study, we reviewed the data of patient's files before treatment, including cancer stage at diagnosis, types of treatments and outcomes. We studied 368 patients treated between 1995 and 2011.

Results: The study included 368 patients (248 [67.4%] males and 120 [32.6%] females) with a median age of 58 (range: 23 - 94). Sixty nine patients (18.8%) had esophageal cancer with a median age of 58.5 years (range: 33 - 84), and 47.8% (33/69) of whom were male. Sixty five (17.7%) were reported to have gastro-esophageal junction (GEJ) with a median age of 62.0 (range: 32 - 94), among them 72.3% (47/65) of whom were male and finally Two hundred thirty four (63.6%) had gastric cancer with a median age of 57.0 (range: 23 - 82), which 71.8% (168/234) of whom were male. The Median follow-up was 10 months. The majority of patients were diagnosed at an advanced stage of disease. Stage III or IV was observed in 65.0% (39/60) of patients with esophageal cancer, 75.0% (33/44) with GEJ cancer and 65.4% (121/185) with gastric cancer. In this study, 58% of patients with esophageal cancer, 50.8% with GEJ and gastric cancers had unresectable disease or metastases at presentation. One-year EFS was 51.8% (95% CI: 39.8 - 67.3%), 32.8% (95% CI: 22.1 - 48.7%), and 56.7% (95% CI: 50.1 - 64.3%) in patients with esophageal, GEJ and gastric cancers, respectively (p = 0.002). The 1-year OS was 54.5% (95% CI: 42.6 - 69.8%), 39.5% (95 CI: 28.1 - 55.5%), and 68.2% (95% CI: 61.8 - 75.3%), respectively (p < 0.001).

Conclusion: Cancers of the upper gastrointestinal (GI) tract contribute to the high mortality and morbidity rates because they are more likely to be diagnosed at late or advanced stages of disease. Cancer of the GEJ has a poor prognosis compared to esophageal and gastric cancers. Moreover, treatment protocols may need improvement to achieve better results.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003437PMC
May 2014

The Effect of GVHD on Long-term Outcomes after Peripheral Blood Allogeneic Stem Cell Transplantation from an HLA-identical Sibling in Adult Acute Lymphocytic Leukemia: A Landmark Analysis Approach in Competing Risks.

Int J Hematol Oncol Stem Cell Res 2014 ;8(2):1-8

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Allogeneic Hematopoietic stem cell transplantation (HSCT) is the most effective therapy to prevent relapse in acute lymphocytic leukemia (ALL). This benefit is affected by non-relapse mortality (NRM) due to complications such as graft versus host disease (GVHD). A new approach in analyzing time-dependent covariates in competing risks is landmark analysis. So, the aim of this study is to evaluate the effect of acute and chronic GVHD on long-term outcomes, relapse and NRM, after allogeneic HSCT in adult ALL using landmark analysis. This study was conducted on 252 ALL patients who were allogeneic transplanted from an HLA-identical sibling with peripheral blood (PB) as the source of stem cell from 2004 to 2012 and were followed-up until 2013. In the first 100 days after transplant, a landmark analysis on days +10, +11, +12, +17, +24, and +31 was applied to assess the effect of acute GVHD on early relapse and NRM. Similarly, for patients alive and event-free at day +100 after transplant, a landmark analysis at time points day +101, months +4, +5, +6, +9, and +12 was applied to evaluate the effect of chronic GVHD on late relapse and NRM. Five-year LFS and OS were 35.0% (95% CI: 29.1, 42.2%) and 37.5% (95% CI: 31.3, 45.0%), respectively. Five-year cumulative incidence of relapse was 44.5% (95% CI: 37.9, 51.0%) while this was 20.4% (95% CI: 15.4, 26.0%) for NRM. The landmark analysis in the first 100 days after transplant showed that the grade III/IV of aGVHD has a lower risk of relapse but higher risk of NRM after adjustment for the EBMT risk score. For patients alive at day +100, cGVHD had no significant effect on relapse. Limited cGVHD had lower risk of NRM and after 6 month post-transplant the risk of NRM decreased and there were not important difference between the groups of cGVHD. Using advanced models enables us to estimate the effects more precisely and ultimately make inference more accurately.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003436PMC
May 2014

Non-TBI hematopoietic stem cell transplantation in pediatric AML patients: a single-center experience.

J Pediatr Hematol Oncol 2013 Aug;35(6):e239-45

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Hematopoietic stem cell transplantation (HSCT) has been established as a promising treatment in acute myeloid leukaemia (AML). Several studies have been performed to minimize the toxicity of HSCT in children without impairing the efficacy. We report our long-term results of HSCT in pediatric AML patients using non-total body irradiation conditioning regimen.

Procedure: From May 1991 to June 2010, 133 pediatric patients with AML (age<15 y) who were referred to our institute underwent autologous (auto-) or allogeneic (allo-) HSCT. The conditioning regimen consisted of oral busulfan plus etoposide in auto-HSCT patients and oral busulfan plus cyclophosphamide in allo-HSCT patients.

Results: Overall survival (OS), leukemia-free survival (LFS), probability of relapse, and transplantation-related mortality at 3 years were 67.6%, 62.2.5%, 27.3%, and 10.1%, respectively. There was no significant difference between allo-HSCT and auto-HSCT groups. In multivariable analysis using Cox proportional hazards regression model, male sex was associated with significantly improved OS (P<0.001) and LFS (P=0.022). An age ≤3 years was associated with higher relapse (P=0.034) and worse OS (P=0.001) and LFS (P=0.014).

Conclusions: The role of allo-HSCT in pediatric AML patients in first complete remission is uncertain. Further randomized studies are recommended to clarify the optimal postremission therapy in these patients.
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http://dx.doi.org/10.1097/MPH.0b013e31827080fcDOI Listing
August 2013

The outcome of allogeneic hematopoietic stem cell transplants without total body irradiation in pediatric patients with acute lymphoblastic leukemia: single centre experience.

J Pediatr Hematol Oncol 2012 Mar;34(2):101-7

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The most widely accepted conditioning regimen to allogeneic hematopoietic stem cell transplantation consists of total body irradiation, especially in patients affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we report our experience on hematopoietic stem cell transplantation in 44 pediatric patients with acute lymphoblastic leukemia using a non-radiation-based conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in complete remission. At a median follow-up of 390 days, the probabilities of 3-year disease-free survival and overall survival were 50% and 68%, respectively. Disease status of hematopoietic stem cell transplantation was the only significant variable affecting the overall survival. Acute and chronic graft-versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively. Relapse was significantly higher among patients transplanted in advanced disease status. The results of the study indicate that non-radiation-based preparative regimens can be used in pediatric patients with ALL. However, well-designed comparative trials are needed to better clarify the difference between radiation and non-radiation-based conditioning regimens in pediatric ALL.
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http://dx.doi.org/10.1097/MPH.0b013e31824435a1DOI Listing
March 2012

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

Hematol Oncol Stem Cell Ther 2011 ;4(3):109-15

Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objective: 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.

Design And Settings: Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center.

Patients And Methods: 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-identical 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.

Results: 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).

Conclusion: Despite the high incidence of acute GVHD (78.6%) in the non-fludarabine group, which resulted 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.
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http://dx.doi.org/10.5144/1658-3876.2011.109DOI Listing
February 2012

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

Arch Iran Med 2011 Sep;14(5):332-4

Hematology Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/008DOI Listing
September 2011

Phase II study of single-agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia.

J Clin Oncol 2011 Jul 6;29(20):2753-7. Epub 2011 Jun 6.

Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Ave, Tehran, Iran.

Purpose: The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high efficacy of single-agent arsenic trioxide in newly diagnosed APL. However, long-term follow-up results are needed.

Patients And Methods: One hundred ninety-seven patients with newly diagnosed APL were treated with arsenic trioxide 0.15 mg/kg daily intravenous infusion until complete remission (CR). After achieving CR, the patients received one to four more courses of therapy with arsenic trioxide as consolidation and were observed with reverse-transcriptase polymerase chain reaction studies from peripheral blood (to detect of minimal residual disease) every 3 months or until relapse or death.

Results: The morphologic CR rate was 85.8%. The most common cause of remission failure was early death owing to APL differentiation syndrome (13.2%). The most important prognostic factor for early mortality was a high WBC count at presentation. The 5-year disease-free survival (DFS) rate was 66.7% ± 4% (SE). Relapse after 5 years in CR was rare. The 5-year overall survival (OS) rate by intention-to-treat analysis was 64.4% ± 4%. In patients who achieved CR, OS and DFS were identical.

Conclusion: The long-term follow-up of newly diagnosed patients with APL treated with single-agent arsenic trioxide shows high rates of DFS and OS.
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http://dx.doi.org/10.1200/JCO.2010.32.2107DOI Listing
July 2011

Frequency, risk factors, and outcome of acute kidney injury following bone marrow transplantation at Dr Shariati Hospital in Tehran.

Iran J Kidney Dis 2010 Jan;4(1):20-6

Nephrology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: 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.

Materials And Methods: 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.

Results: 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.

Conclusions: 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.
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January 2010

Stem cell transplantation; Iranian experience.

Arch Iran Med 2009 Jan;12(1):69-72

Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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January 2009

The prevalence of low selenium levels in adult patients undergoing bone marrow transplantation: a brief communication.

Nutr Cancer 2008 ;60(6):837-9

Faculty of Pharmacy, Medical Sciences, University of Tehran, Tehran, Iran.

Selenium (Se) is an essential trace element, and its deficiency is considered to be important in various types of cancer. There are just a few data regarding this issue among adult patients with hematological malignancy. Serum Se levels were determined in 22 adult patients candidates for bone marrow transplantation (BMT) in Iran. The mean serum Se levels before BMT was 19.91 microg/l (from 12.00 to 62.00 microg/l), and almost all the patients had low Se serum levels (normal serum Se level: 46-143 microg/l). The level of Se 20 days after BMT was 22.53 microg/l, which did not show any significant changes. Most of the patients did not suffer from malnutrition, as they had mostly normal albumin levels. Even though the results of this study showed that Se deficiency is common among our hematological malignant patients, it can not be concluded that these low Se levels are causally related to cancers for which BMT is undertaken. Further studies are needed to evaluate the Se levels at diagnosis before treatment effects.
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http://dx.doi.org/10.1080/01635580802196107DOI Listing
February 2009

Hematopoietic stem cell transplantation in Iran: 1991 to 2008.

Hematol Oncol Stem Cell Ther 2008 Oct-Dec;1(4):231-8

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Dr. Shariati Hospital, Tehran, Iran.

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.
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http://dx.doi.org/10.1016/s1658-3876(08)50010-0DOI Listing
May 2010

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

Arch Iran Med 2008 May;11(3):247-51

Hematology-Oncology and Bone Marrow Transplant Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: 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.

Methods: 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).

Results: 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%.

Conclusion: 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.
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http://dx.doi.org/08113/AIM.003DOI Listing
May 2008

Continuous bladder irrigation prevents hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

Urol Oncol 2008 Jan-Feb;26(1):43-6. Epub 2007 Nov 7.

Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Hemorrhagic cystitis is 1 of the most troublesome complications of hematopoietic cell transplantation conditioning regimens. We conducted a nonrandomized controlled clinical study to investigate the role of continuous bladder irrigation in addition to mesna, hydration, and alkalization in the prevention of hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. A total of 80 eligible patients entered the study. From May 2006, 40 patients who underwent allogeneic hematopoietic cell transplantation received continuous bladder irrigation in addition to the common protocol. A historical control group of 40 consecutive patients with same inclusion criteria who did not receive bladder irrigation was enrolled from before May 2006. Hemorrhagic cystitis occurred in 50% of patients in the no bladder irrigation group versus 32% in bladder irrigation group (P = 0.11). The mean duration of hemorrhagic cystitis was significantly reduced in the bladder irrigation group (10 vs. 18 days; P = 0.02). Duration of hospitalization was significantly shorter in the bladder irrigation group (30.2 vs. 39.6; P < 0.001). Late-onset hemorrhagic cystitis that occurred beyond 4 weeks after allo-hemorrhagic cystitis happened more significantly in the no bladder irrigation group (P = 0.001). High-grade hemorrhagic cystitis was more frequently associated with high-grade graft-versus-host disease within 30 days after transplant (P = 0.06). In general, continuous bladder irrigation added to mesna, hydration, and alkalization regimens was well tolerated, decreased the complications of hemorrhagic cystitis, and may be useful in hematopoietic cell transplantation patients. However, more investigations with randomized controlled clinical trials with more patients are needed.
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http://dx.doi.org/10.1016/j.urolonc.2006.12.015DOI Listing
February 2008

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

Arch Iran Med 2006 Apr;9(2):99-103

Hematology-Oncology and BMT Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The coexistence of recipient's and donor's hematopoietic systems after allogeneic marrow transplantation is called mixed chimerism.

Objective: The objective of this study was to evaluate the effects of MC on graft-versus-host disease (GVHD), disease recurrence, and survival after HLA identical marrow transplantation in a transplant center in Iran.

Methods: The association of MC with acute GVHD, disease recurrence, survival, and relapse-free survival was investigated in 91 patients who underwent either bone (n = 12) or peripheral blood (n = 79) HLA-identical marrow transplantation. Chimerism was assessed using multiplex amplification of short tandem repeats (STR). Patients had thalassemia (n = 19), acute myelogenous leukemia (AML) (n = 29), acute lymphocytic leukemia (ALL) (n = 20), chronic myelogenous leukemia (CML) (n = 18), and other diseases (n = 5). The median age was 21 (range: 3 - 50) years. There were 38 (42%) female and 53 (58%) male participants. Conditioning was made through busulfan plus cyclophosphamide in 34 patients; busulfan plus fludarabin in 51 patients; and busulfan plus fludarabin plus antithymocyte globulin in 6 patients. The median follow-up was 13 months.

Results: On day +30, complete chimerism (CC) was observed in 72 (79%) patients, MC in 15 (17%), and no chimerism in 4 patients. The incidence of acute GVHD was significantly (P = 0.01) lower in mixed chimeras than in complete chimeras. There was no significant difference in acute GVHD grade (I, II vs. III, IV) between the two groups. The incidence of relapse was 18%. There was no difference in relapse rate between MC and CC groups. Overall survival was 89%. There was no significant difference in the overall survival between MC and CC group (96% vs. 85%, respectively). Relapse-free survival was 80% that was not significantly different between the two groups.

Conclusion: Despite some previous reports, we found no significant difference in the survival and relapse rates between MC and CC groups.
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April 2006