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Posterior Reversible Encephalopathy Syndrome in Pediatric Hematopoietic Stem Cell Transplantation with Beta Major Thalassemia: The Association between the PRES Occurrence and Class of Beta Major Thalassemia
Jafari, L., Behfar, M., Tabatabaie, S., Karamlou, Y., Kashani, H., Radmard, A. R., Mohseni, R., Naji, P., Ghanbari, F., Ashkevari, P., et al
Clinical transplantation. 2023;:e15164
Abstract
INTRODUCTION Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive curative option for β-major thalassemia patients (β-MT). Posterior reversible encephalopathy syndrome (PRES) is a pervasive neurological complication which typically occurs following HSCT. β-MT patients are prone to a higher PRES incidence due to long-term immunosuppression; thus, it is imperative that these patients are closely monitored for PRES after HSCT. PATIENTS AND METHODS We included 148 pediatric patients with β-MT who underwent HSCT between March 2015 and August 2022 in Children's Medical Center. Patients in this study were divided into two groups. The association between PRES and class of β-MT and other risk factors were assessed and the overall survival rate was determined. RESULTS Fourteen out of 112 patients (12%) with class I and II β-MT developed PRES. However, PRES occurred in 11 out of 36 patients (30.5%) with β-MT-III. Our results indicated that there was a significant association between class III β-MT and the occurrence of (P = .004). Additionally, acute graft-versus-host disease (aGVHD) occurred in 80% and 44.7% of patients in the PRES and non-PRES groups, respectively (P = .001). The results of the Kaplan-Meier analysis revealed that the 5-year overall survival (OS) was 75.6% in the PRES group versus 95% in the non-PRES group, which was statistically significant (P = .001). CONCLUSION Based on our results, pediatric β-MT III patients are at a higher risk of developing PRES. Additionally, pediatric β-MT patients with a history of aGVHD, regardless of disease class, are more likely to develop PRES. Considering these results, PRES has a higher chance of being the etiology of symptoms and should be considered more often in these patients.
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A comprehensive comparison between TBI vs non-TBI-based conditioning regimen in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis
Ansari, F., Behfar, M., Jafari, L., Mohseni, R., Naji, P., Karamlou, Y., Amirzade-Iranaq, M. H., Hamidieh, A. A.
Leukemia research. 2023;135:107416
Abstract
INTRODUCTION We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric patients (under 18 years old) with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS A systematic search was performed on MEDLINE, Scopus, WOS, and PMC. Also, a search for grey literature was performed on Google Scholar and relevant articles' references were included. Relevant articles which met the inclusion criteria were retrieved up to October 31th, 2022. CMA version 2 was used for the quantitative synthesis of the data. RESULTS Eight studies on efficacy and safety of TBI and non-TBI as a conditioning regimen were analyzed and six comparative studies on late toxicity were investigated. The meta-analysis revealed a hazard ratio (HR) of 1.508 (95% CI 0.96-2.35) for overall survival (OS) in instances of non-TBI conditioning. Also, an HR of 1.503 (95% CI 1.006-2.25) for disease-free- survival (DFS) favoring TBI-based conditioning. Late complications were reported to be significantly higher in the TBI conditioning regimen group than in the non-TBI group. CONCLUSION It appears that non-TBI regimens are as effective as TBI regimens in pediatrics with ALL regarding OS. Occurrence of latent toxicity is higher with TBI conditioning regimen. Conversely, TBI-based regimens are superior to non-TBI conditioning regimens regarding DFS. Considering all aspects, non-TBI conditioning regimens can be an alternative treatment option for pediatric ALL undergoing HSCT.
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Fanconi anemia phenotypic and transplant outcomes' associations in Iranian patients
Ansari, F., Behfar, M., Naji, P., Darvish, Z., Rostami, T., Mohseni, R., Alimoghaddam, K., Salajegheh, P., Ahadi, B., Mardani, M., et al
Health science reports. 2023;6(4):e1180
Abstract
OBJECTIVES Fanconi anemia (FA) is a rare, heterogeneous, inherited disorder. Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only therapeutic option to restore normal hematopoiesis. This study reports the outcomes of FA-HSCT patients and identifies factors, including clinical phenotype. Our team examined more than 95% of Iranian FA patients during the last decade. STUDY DESIGN One hundred and six FA patients (age range: 2-41) who underwent HSCT from March 2007 to February 2018 were enrolled. Clinical characteristics of genetic disease, pre-HSCT findings, HSCT indication, and long-term follow-up evaluated and recorded. Data were analyzed using SPSS 19.0. RESULTS The mean follow-up period for survivors was 36 months (range, 1-101). The 3-year overall survival (OS) and disease-free survival were 72.2% and 71.2%, respectively. The 3-year OS rate for patients with limited and extensive malformations was 78.8% and 56.6%, respectively (p = 0.025). Acute graft versus host disease incidence was 60.52% for patients with limited malformations versus 70% for patients with extensive ones (p = 0.49). Chronic graft versus host disease incidence for these two groups was 9.21% and 10%, respectively (p = 0.91). CONCLUSIONS OS was not associated with each of the malformations singly; however, it was lower in the extensive group. The younger age of patients at the HSCT time leads to a higher OS. The differences in FA patients' outcomes and the various genotypes were probably related. These data provide a powerful tool for further studies on genotype-phenotype association with HSCT results.
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Risk factors for a severe disease course in children with SARS-COV-2 infection following hematopoietic cell transplantation in the pre-Omicron period: a prospective multinational Infectious Disease Working Party from the European Society for Blood and Marrow Transplantation group (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH) study
Averbuch, D., de la Camara, R., Tridello, G., Knelange, N. S., Bykova, T. A., Ifversen, M., Dobsinska, V., Ayas, M., Hamidieh, A. A., Pichler, H., et al
Bone marrow transplantation. 2023;:1-9
Abstract
Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.
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Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey
Iida, M., Liu, K., Huang, X. J., Huang, H., Kuwatsuka, Y., Moon, J. H., Lee, J. W., Lakshmi, K. M., Dodds, A., Wilcox, L., et al
Blood cell therapy. 2023;6(4):114-123
Abstract
The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.
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Total body irradiation-free haploidentical peripheral blood stem cell transplantation compared to related and unrelated donor transplantation in pediatrics with acute lymphoblastic leukemia
Mardani, M., Behfar, M., Jafari, L., Mohseni, R., Naji, P., Salajegheh, P., Donyadideh, G., Hamidieh, A. A.
Pediatric blood & cancer. 2023;:e30255
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Editor's Choice
Abstract
BACKGROUND Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer under the age of 15 years. Despite the recent advances in therapeutic regimens, relapse occurs in 15%-20% of pediatric patients after chemotherapy, and hematopoietic stem cell transplantation (HSCT) is the best treatment option. However, donor availability is one of the major challenges. Over the last decade, haploidentical donor (HID) transplantation has evolved as an alternative option. Herein, we aimed to compare the transplant outcomes in pediatric patients receiving total body irradiation (TBI)-free myeloablative regimens, between non-HID and HID transplant. PATIENTS AND METHODS The study included 60 pediatric ALL patients who had undergone HSCT from October 2016 until September 2020. Forty-three patients received non-HID HSCT, while 17 patients received HID. The sources of stem cells (SC) were peripheral blood stem cells (PBSC) for all the patients. The conditioning regimen was based on busulfan and cyclophosphamide. For graft-versus-host disease (GvHD) prophylaxis, patients received cyclosporine and methotrexate in the setting of non-HID transplantation, where HIDs received post-transplant cyclosporine and cyclophosphamide. RESULTS The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for matched sibling donor-matched related donor (MSD-MRD), matched unrelated donor-mismatched unrelated donor (MUD-MMUD), and HID groups, respectively (p = .85). The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively (p = .47). Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45% (p = .64). The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant (p = .55). There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs (p < .01). CONCLUSION Our results indicate that PBSC-HID transplant outcomes in the setting of non-TBI conditioning are comparable to those of non-HIDs in pediatric ALL patients.
PICO Summary
Population
Children with acute lymphoblastic leukaemia undergoing transplant at a single centre in Iran (n=60)
Intervention
Matched sibling donor or matched related donor (MSD-MRD, n=31); Matched unrelated donor or mismatched unrelated donor (MUD-MMUD, n=12)
Comparison
Haploidentical donor (HID, n=17)
Outcome
The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for MSD-MRD, MUD-MMUD, and HID groups, respectively. The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively. Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45%. The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant. There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs.
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The Effect of Early BCG-Vaccination of SCID Pediatric Patients on the Outcome of Hematopoietic Stem Cell Transplantation Using Reduced Conditioning Regimen
Hamidieh, A. A., Jafari, L., Behfar, M., Karamlou, Y., Shamsipour, M., Mohseni, R., Farajifard, H., Salajegheh, P.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND The eminence of Bacillus Calmette-Guerin (BCG) vaccine in the vaccination program of newborns, especially in low-income developing countries where tuberculosis is prevalent, has been conspicuous throughout the years; however, the application of the aforementioned vaccine is not without constraints, especially in patients afflicted with immunodeficiency diseases, such as Severe Combined Immunodeficiency (SCID). OBJECTIVE The desideratum of this study is to evaluate whether or not the administration of BCG vaccine upon birth could attenuate the success of hematopoietic stem cell transplantation (HSCT) in SCID pediatric patients STUDY DESIGN In the current study, 30 SCID patients who underwent HSCT using reduced intensity conditioning regimen (RIC) were followed-up for 2 years post-HSCT. The outcome of HSCT was evaluated in both non-BCG-vaccinated (12 patients) and BCG-vaccinated (18 patients) groups. RESULTS Our results demonstrated that patients who had been BCG vaccinated displayed higher incidences of acute GvHD (aGvHD); however, the incidence of chronic GvHD did not differ between the two groups. The overall survival (OS) rate in patients who received the BCG vaccine was similar than their non-vaccinated counterparts. We speculate that the reason that BCG-vaccinated individuals' survival rate, despite having the risk factor of being BGC-vaccinated, was similar to the non-BCG-vaccinated group was due to the fact that they received RIC as their conditioning regimen. CONCLUSION The result of our study indicated that early BCG vaccination was associated with a higher risk of aGVHD. Additionally, the OS of BCG-vaccinated patients was similar in comparison to their non-vaccinated counterparts; alluding to the possibility that the same RIC regimen might be the reason for such outcome, since no other variation between the two groups existed. Regarding to the BCG vaccine affect the outcome of HSCT, we suggest that the administration of BCG vaccine should be deferred until three months of age so that apt testing, without the interference of maternal antibodies, could be performed; however, it is noteworthy that this study could benefit from a bigger cohort in order to further validate the outcome, as the possible reason for some factors not becoming statistically significant was the small sample size of this study.
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Trends in disease indications for hematopoietic stem cell transplantation in the Asia-Pacific region: A report of the Activity Survey 2017 from APBMT
Iida, M., Liu, K., Huang, X. J., Depei, W., Kuwatsuka, Y., Moon, J. H., Dodds, A., Wilcox, L., Ko, B. S., Hamidieh, A. A., et al
Blood cell therapy. 2022;5(4):87-98
Abstract
The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.
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Radiation-free myeloablative allogeneic hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia: A comparison of outcomes between patients with and without central nervous system involvement
Esfandbod, M., Enshaei, M., Monzavi, S. M., Kabootari, M., Behfar, M., Hamidieh, A. A.
Leukemia Research. 2021;111:106703
Abstract
For patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), total body irradiation (TBI) has been particularly advocated as a part of the conditioning regimen in case of extramedullary involvement in sanctuary sites such as the central nervous system (CNS), to ensure greater tissue penetration. In resource-limited countries lacking TBI facilities; however, ALL patients undergo radiation-free myeloablative conditioning, though its impacts on post-HSCT outcomes of the patients with pre-HSCT CNS involvement have not been analyzed. In this 14-year series of 278 adult (> 18 y) ALL patients undergoing TBI-free busulfan/cyclophosphamide conditioning allo-HSCT, we found that the long-term probabilities of overall survival, disease free survival, relapse and non-relapse mortality were not significantly different between CNS-involved and CNS-spared patients. Moreover, there was no statistically significant difference in the incidence of post-HSCT CNS relapse between CNS-involved and CNS-spared patients. Pre-HSCT cranial radiation therapy (CRT) showed no significant preventive effect on the likelihood of post-HSCT CNS relapse. Through multivariable regression analysis, grade III-IV acute graft-versus-host disease (GvHD), extensive chronic GvHD and post-HSCT relapse were ascertained as independent determinants of mortality (Adj.R(2) = 53.9 %, F((12,265)) = 28.1, P < 0.001), while other parameters including Philadelphia translocation, pre-HSCT CNS involvement and CRT were found to have no independent effect. Although this study was not an attempt to compare TBI-based vs. non-TBI conditioning, the TBI-free myeloablative allo-HSCT was shown to be feasible and an option for adult ALL patients with CNS involvement, considering the comparable outcomes between patients with and without CNS involvement.
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One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors
Niederwieser, D., Baldomero, H., Bazuaye, N., Bupp, C., Chaudhri, N., Corbacioglu, S., Elhaddad, A., Frutos, C., Galeano, S., Hamad, N., et al
Haematologica. 2021
Abstract
The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCTs were reported from 1662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous and 7.0% in allogeneic HCT and bringing the total to 1,298,897 procedures. Assuming a frequency of 84,000/year, 1.5 million HCTs had been performed by 2019 from 1957. Slightly more autologous (53.5%) than allogeneic and more related (53.6%) than unrelated HCTs were reported. A remarkable increase was noted in haploidentical related HCT for leukemias and lymphoproliferative diseases, but even more in non-malignant diseases. Transplant rates (TR; HCT/10 million population) varied according to region reaching 560.8 in North America, 438.5 in Europe, 76.7 in Latin America, 53.6 in South East Asia/Western Pacific (SEA/WPR) and 27.8 in African/East Mediterranean (AFR/EMR). Interestingly, haploidentical TR amounted to 32% in SEA/WPR and 26% in Latin America, but only 14% in Europe and EMR and 4.9% in North America of all allogeneic HCT. HCT team density (teams/10 million population) was highest in Europe (7.7) followed by North America (6.0), SEA/WPR (1.9), Latin America (1.6) and AFR/EMR (0.4). HCTs are increasing steadily worldwide with narrowing gaps between regions and greater increase in allogeneic compared to autologous activity. While related HCT is rising, largely due to increase in haploidentical HCT, unrelated is plateauing and cord blood in decline.