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1.
Comparable Outcomes of Pre- Versus Post-Tyrosine Kinase Inhibitor Era Treatment in Chronic Myeloid Leukemia: A Retrospective Cohort Study With Long-term Follow-up
Tavakoli, S., Khalaj, F., Kasaeian, A., Mousavi, S. A., Mousavian, A. H., Arabi, F., Rad, S., Rostami, S., Barkhordar, M., Biglari, M., et al
Cell transplantation. 2023;32:9636897231163212
Abstract
Imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was introduced after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia (CML). However, the long-term effects of allo-HSCT in chronic phase CML patients are mostly unknown. We retrospectively analyzed the outcomes of 204 patients with sibling donors who received peripheral stem cells and underwent allo-HSCT of chronic phase I (CP1) in the pre- and post-TKI era at Shariati Hospital in Tehran, Iran, from 1998 to 2017 and followed up till the end of 2021. The median follow-up time for all patients was 8.7 (SD = 0.54) years. Fifteen-year overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM) incidence were 65.70%, 57.83%, 17.56%, 13.17%, and 28.98%, respectively. Using multivariable analyses, the only risk factor increasing the hazard of death was the time between diagnosis to allo-HSCT greater than 1 year compared to this time less than 1 year by 74% [hazard ratio (HR) = 1.74, P = 0.039]. Also, age is a significant risk factor for DFS (HR = 1.03, P = 0.031). Our findings suggested that allo-HSCT is still an important treatment option for CP1 patients, especially those resistant to TKI treatment. TKI consumption can have a desirable effect on NRM after allo-HSCT for CP1 CML.
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2.
A Comparison of Dexamethasone Plus Vincristine versus Standard Regimen in Induction Therapy of Adult Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplantation
Vaezi, M., Pourkhani, A., Kasaeian, A., Souri, M., Yaghmaie, M., Chardouli, B., Alimoghaddam, K., Ghavamzadeh, A.
International journal of hematology-oncology and stem cell research. 2022;16(1):22-33
Abstract
Background: Current treatment options of acute lymphoblastic leukemia(ALL) include chemotherapy alone or hematopoietic stem cell transplantation (HSCT) following induction chemotherapy both along with CNS prophylaxis. The usual and standard induction regimens currently administered could have severe complications and mortality. Materials and Methods: To lessen induction regimen complications in ALL patients who undergo HSCT, we used a cytoreduction induction regimen including dexamethasone (8 mg, IV, three times a day, for 28 days) and vincristine(1.4 mg/m(2), IV, on days 1,8,15 and 22) for 49 newly diagnosed adult ALL patients followed by an early sibling donor HSCT within two months. The results were matched with outcomes of HSCT in 172 ALL patients inducted by standard induction regimen. Results: Median follow-up time was 5.41 years in the standard group and 5.27 years in the other. All patients of the case group (100%) achieved complete remission. Landmark analyses were performed to scrutinize the effect of treatments on different time intervals: first two years and 2(nd) to end years. Type of treatment had no significant effect on the hazard of death in the first landmark (HR=0.87, P=0.64). Cytoreduction regimen amplified the hazard of death 3.43 times more than the standard regimen in the second landmark (HR=3.43 P=0.035). Multivariate analysis showed that the cytoreduction regimen reduced the hazard of relapse about 22%, but not statistically significant (HR=0.78, P-value=0.24). Conclusion: Overall, it seems despite achieving complete remission in induction therapy, depth of response is a critical predictor for long-term outcomes of HSCT in ALL patients, and the use of multiple agents may be necessary to decrease tumor cell burden and minimal residual disease(MRD).
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3.
Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia
Barkhordar, M., Kasaeian, A., Janbabai, G., Kamranzadeh Fumani, H., Tavakoli, S., Rashidi, A. A., Mousavi, S. A., Ghavamzadeh, A., Vaezi, M.
Frontiers in immunology. 2022;13:921293
Abstract
In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg/kg/day, on days -3, -2, and -1) and PTCy (40 mg/kg/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg/kg/day from days -4 to -1) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II-IV and III-IV and extensive chronic GvHD were considerably lower in the ATG/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome.
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4.
Outcomes of haploidentical peripheral stem cell transplantation with combination of post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) compared to unrelated donor transplantation in acute myeloid leukemia: A retrospective 10-year experience
Barkhordar, M., Kasaeian, A., Janbabai, G., Mousavi, S. A., Fumani, H. K., Tavakoli, S., Bahri, T., Ghavamzadeh, A., Vaezi, M.
Leukemia research. 2022;120:106918
Abstract
In the evolution of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), In vivo T-cell modulation with concomitant use of anti-thymocyte globulin (ATG) and high-dose post-transplant cyclophosphamide (PTCy) provides a novel promising method on transplant outcomes; however, the long-term effects of this therapy are mostly unknown. We retrospectively compared the long-term outcomes of adult acute myeloid leukemia (AML) patients undergoing a haplo-HSCT (n = 92) with a new modified combination of ATG and PTCy in the context of peripheral blood stem cell (PBSC) and myeloablative conditioning (MAC) with an otherwise similar group of AML patients who received an unrelated donor (URD) HSCT (n = 57) with ATG protocol from February 2010 to December 2020 at our single-center (HORCSCT). Median follow-up was 3.73 and 4.28 years for haploidentical and URD-HSCT, respectively. In haplo-HSCT, the cumulative incidence of grades II-IV and III-IV acute graft versus host disease (aGvHD) and extensive chronic GvHD (cGvHD) was much lower than in URD (27% versus 56% for grades II-IV, 8.7% versus 24.5% for grades III-IV, and 15.4% versus 34.7% for extensive cGvHD, respectively). Five-year overall survival (OS) was 54.03% for haplo and 54.48% for URD (p = 0.927); GvHD-free relapse-free survival (GRFS) was 44.1% and 29.86% (p = 0.149); relapse incidence was 15.79% and 26.95% (p = 0.72); and non-relapse mortality (NRM) was 29.48% and 26.32% (p = 0.73), respectively. Using multivariable analyses, when compared to Haplo, URD was a significant predictor of relapse (HR=1.80, p = 0.039); however, no difference in OS, GRFS, and NRM was noted between haplo and URD. Therefore, given the favorable results with haplo-HSCT and considering donor availability promptly with low cost, it conservatively suggested that haplo-HSCT with the introduced protocol could be viewed as the first alternative for patients with AML in the absence of matched sibling donors.
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5.
Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
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6.
Trends in patient outcome over the past two decades following allogeneic stem cell transplantation for acute myeloid leukemia. An ALWP/EBMT analysis
Canaani, J., Beohou, E., Labopin, M., Ghavamzadeh, A., Beelen, D., Hamladji, R. M., Niederwieser, D., Volin, L., Markiewicz, M., Arnold, R., et al
Journal of internal medicine. 2018
Abstract
BACKGROUND Outcomes for patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo-SCT) have significantly improved in recent years. OBJECTIVES To assess the incremental improvement of transplanted AML patients in the last two decades. METHODS Patients included in this analysis were adult AML patients who underwent allo-SCT from an HLA matched sibling donor (MSD) or matched unrelated donor (MUD) in first remission. Patient outcomes were assessed between three cohorts according to the year of transplant (1993-2002, 2003-2007, and 2008-2012). RESULTS The analysis comprised a total of 20187 patients of whom 4763 were transplanted between 1993-2002, 5835 in 2003-2007, and 9589 in 2008-2012. In multivariate analysis, leukemia free survival (LFS) rates were significantly improved in more recently transplanted patients compared to patients transplanted in 1993-2002 [Hazard ratio (HR)=0.84, confidence interval (CI) 95%, 0.77-0.92; P=0.003], a benefit which also extended to improved overall survival (OS) (HR=0.8, CI 95%, 0.73-0.89; P<0.0001), and decreased non-relapse mortality (NRM) rates (HR=0.65, CI 95%, 0.56-0.75; P<0.0001). Subset analysis revealed that in MSD, the rates of LFS, NRM, and OS significantly improved in patients in the more recent cohort with similar results also seen in MUD. Finally, the incidence of acute graft versus host disease (GVHD) was significantly reduced leading to improved GVHD-free/relapse-free survival (GRFS) rates in more recently transplanted patients. CONCLUSION Outcome of allo-SCT for AML patients has markedly improved in the last two decades owing to decreased non-relapse mortality and improved rates of leukemia-free survival resulting in significantly longer survival. This article is protected by copyright. All rights reserved.
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7.
Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Salvatore, D., Labopin, M., Ruggeri, A., Battipaglia, G., Ghavamzadeh, A., Ciceri, F., Blaise, D., Arcese, W., Socie, G., Bourhis, J. H., et al
Haematologica. 2018
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Editor's Choice
Abstract
Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated haploidentical to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were int- and high-risk acute myeloid leukemia in first complete remission undergoing haploidentical and matched sibling donor transplant from 2007-2015 and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donor were matched with 1 haplo. We identified 2654 pts (haplo =185; matched sibling donor =2469), 2010 with intermediate- acute myeloid leukemia (haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (haplo =63; matched sibling donor =581). Median follow up was 30 (range 1-116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, haplo resulted in lower leukemia-free-survival (Hazard Ratio 1.74; p<0.01), overall-survival (HR 1.80; p<0.01) and GVH-free-relapse-free-survival (Hazard Ratio 1.32; p<0.05) and higher non-relapse-mortality (Hazard Ratio 3.03; p<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free-sruvival, overall-survival and GVH-free-relapse-free-survival according to donor type. Higher grade II-IV acute graft versus host disease was observed for haplo in both high-risk (Hazard Ratio 2.20; p<0.01) and int-risk (Hazard Ratio 1.84; p<0.01). A trend for a lower Relapse-Incidence was observed in haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; p=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.
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A Single-Center Experience With Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia: A Modest Pitch for Non-Total Body Irradiation Conditioning Regimens
Hamidieh, A. A., Eslami Shahre Babaki, A., Rostami, T., Kasaeian, A., Koochakzadeh, L., Sharifi Aliabadi, L., Behfar, M., Ghavamzadeh, A.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2018
Abstract
OBJECTIVES Allogeneic hematopoietic stem cell transplantation has been used for several decades to treat patients with acute lymphoblastic leukemia. Total body irradiation has been promoted as an important component of conditioning regimens for this process; however, recent reports of chemotherapy-based conditioning regimens have shown comparable outcomes. MATERIALS AND METHODS We report our experience with radiation-free conditioning using busulfan and cyclophosphamide in 127 pediatric patients with acute lymphoblastic leukemia who were treated between 1997 and 2014. The median age was 11 years (range, < 1 to 15 y), 70% of patients were male, 81.1% received transplants from HLA-matched siblings, 83% received peripheral blood stem cells, 41% were in second complete remission at the time of transplant, and 83% had B-lineage immunophenotype. RESULTS In patients who were in complete remission at the time of transplant, 5-year overall survival, leukemia-free survival, and relapse rates were 62.48% (95% confidence interval, 52.29-71.09%), 49.43% (95% confidence interval, 39.57-58.53%), and 45.64% (95% confidence interval, 35.85-54.88%), respectively. We observed significant differences between outcomes in patients by time of transplant, presence of chronic graft-versus-host disease, and remission status. CONCLUSIONS Our relapse rates were comparable to those shown in recent studies, although the transplant-related mortality rate was lower. The results of our study showed that a busulfan/cyclophosphamide conditioning regimen has acceptable outcomes without the undesirable adverse effects of total body irradiation, particularly in pediatric patients. Large multicenter studies are needed to assess less toxic conditioning regimens with fewer adverse effects in these patients.
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9.
The effects of lower CD34 yields after lowe dose G-CSF induction on long-term autologous stem cell transplantation outcome: A single center study
Vaezi, M., Shakouri, M., Souri, M., Setaredan, M. A., Mossavi, S. A., Mohammadi, S., Alimoghaddam, K., Ghavamzadeh, A.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2018
Abstract
Peripheral blood stem cell transplantation (PBSCT) is an effective treatment for hematological malignancies. Mobilization of peripheral blood stem cells performs in different ways among transplantation centers. Since the Effects of lower CD34+ cells dose after low dose G-CSF induction on autologous stem cell transplantation outcomes are not studied much, so this study was performed for this purpose. 735 autologous stem cell transplanted patients with diagnoses of multiple myeloma (n=330), Hodgkin lymphoma (n=200), non-Hodgkin lymphoma (n=129), acute myeloid leukemia (n=54) and solid tumors (n=22) were retrospectively evaluated. G-CSF was administered at the dose of 5mug/kg/day during mobilization and all patients except acute myeloid leukemia received 10mug/kg/day on the last day. Peripheral blood stem cells were harvested in one session for all patients. The amount of injected CD34+ cells/kg for patients were divided and studied in four groups: <0.5x10(6) (n=36), 0.5-1.0x10(6), (n=132), 1.0-2.0x10(6) (n=226) and >2.0x10(6) (n=305). The median time of follow up was 26.9 months. The amount of CD34+ cells dose were a significant predictor of platelet engraftment, but overall survival, relapse-free survival and also relapse rate was not associated with cells yield. More platelet transfusion (P=0.003) and antibiotics prescription (P=0.001) in transplanted patients with lower CD34 cells dose should be balanced with risks of higher G-CSF doses administration and also its side effects. Our results declare that lower CD34 yields after lowe dose G-CSF induction are probably not a troublesome issue affecting transplantation outcomes.
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10.
FLT3-ITD compared with DNMT3A R882 mutation is a more powerful independent inferior prognostic factor in adult AML patients after Allogeneic Hematopoietic Stem Cell Transplantation: A retrospective cohort study
Ardestani, M. T., Kazemi, A., Chahardouli, B., Mohammadi, S., Nikbakht, M., Rostami, S., Jalili, M., Vaezi, M., Alimoghaddam, K., Ghavamzadeh, A.
Turkish journal of haematology : official journal of Turkish Society of Haematology. 2018
Abstract
OBJECTIVE To identify DNMT3A exon 23 mutations and their prognostic impact in the presence of FLT3-ITD and NPM1 mutations in acute myeloid leukemia (AML) patients treated with Allo-HSCT. MATERIALS AND METHODS This study analyzed128 adult AML patients referred to the Hematology-Oncology & Stem Cell Research Center of Shariati hospital. FLT3-ITD and NPM1 mutations were detected using fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing. Survival curves were estimated by the Kaplan-Meier method and the differences between groups were compared using Log-Rank test. RESULTS The incidence of DNMT3A exon 23 mutations was 15.6% and the hotspot region R882 mutations were prominent. Overall survival (OS) and Relapse-free survival (RFS) were compared in patients with and without DNMT3A exon 23 mutations using univariate analysis and there was no significant difference between two groups of patients. On the contrary, the FLT3-ITD mutation significantly reduced the OS (p=0.009) and RFS (p=0.006) rates in AML patients after allogeneic hematopoietic cell transplantation (Allo-HSCT). In the next step, AML patients were divided into four groups according to DNMT3A and FLT3-ITD mutations. Patients with DNMT3A R882mut/FLT3-ITDpos had the worst OS and RFS. These results indicate that DNMT3A mutations alone cannot affect the clinical outcomes of AML patients treated with Allo-HSCT, but when accompanied by FLT3-ITD mutations, the overall survival was significantly reduced (5-year OS 0% for DNMT3AR882mut/FLT3-ITDpos patients vs 62% DNMT3AR882wt/FLT3-ITDneg, p=0.025) and relapse incidence rate increased. CONCLUSION It can be deduced that DNT3A R882mut/ FLT3-ITDpos is a poor prognostic factor in AML patients even after Allo-HSCT.