Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Bone marrow transplantation. 2020
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.
Posterior Reversible Encephalopathy Syndrome after Allogeneic Stem Cell Transplantation in Pediatric Patients with Fanconi Anemia, a Prospective Study
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurologic complications following hematopoietic stem cell transplantation (HSCT). We aimed to evaluate incidence, clinical, and imaging features of PRES in pediatric patients with FA following HSCT. This prospective study was carried out on all post-HSCT patients with underlying FA disease between 2014 and 2017. Brain CT scan and MRI were performed in all individuals who developed neurologic symptoms. The diagnosis of PRES had done based on clinic-radiological evidence. Follow-up MRI was carried out in all patients with PRES within two months. Forty-one patients with FA (28 males, mean age: 8.19±3.25 years) were enrolled. Out of 15 patients with acute neurologic symptoms, PRES was diagnosed in 9 individuals (21.95%). The occurrence of PRES was significantly higher among patients who had a donor with a one-locus mismatch (p-value: 0.02). Donor relation, stem cell source, and GvHD grading did not have any significant association with the development of PRES. MRI showed asymmetric vasogenic edema in five patients, overt infarct in one, and foci of micro-hemorrhage in three individuals that one of them developing hemorrhagic infarct. The patient expired shortly, while persistent micro-hemorrhage was noted on the other two patients. The result of our study demonstrated the risk of developing PRES after HSCT is higher in FA compared to other diseases reported in articles (21.95% vs. 1-10%), and in contrast to its term, it might be irreversible and has adverse effects on the results of HSCT. Increased vascular and endothelial fragility in FA may impact on the higher frequency of PRES in these individuals.
Analysis of determinant factors of liver fibrosis progression in ex-thalassemic patients
International journal of hematology. 2020
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) potentially renders thalassemia patients disease-free with presumably cessation of associated complications. This study analyzes the liver fibrosis status and the determinants of its progression in ex-thalassemic patients. The liver fibrosis status of 108 pediatric transfusion-dependent ß-thalassemia major patients was evaluated before and one year after allo-HSCT using transient elastography (TE). All patients achieved normal hematopoiesis. In univariate analyses, not in all, but in patients developing significant post-HSCT iron overload or hepatic graft-versus-host disease (GvHD), as well as recipients of bone marrow stem cells (BMSC), significant TE increment occurred. In multivariable analyses, through a model with large effect size (Adj.R(2)?=?26%, F((3,104))?=?13.53, P?0.001), post-HSCT serum ferritin and hepatic GvHD were ascertained as independent determinants of significant TE increase, and the effect of stem cell graft source approached the level of significance. Excluding the patients with intermediate/high Lucarelli risk classes, the TE increase was significantly greater only in BMSC recipients (P?=?0.033). Although the risk impact of allograft source on liver fibrosis progression requires further evaluation; hepatic status of ex-thalassemic patients can be preserved after HSCT, if hepatic GvHD is controlled and adequate post-transplantation iron depletion is ensured.
High prevalence of latent tuberculosis in hematopoietic stem cell transplant recipients: A First Report
Pediatric transplantation. 2020;:e13770
TB is an increasing health problem, and patients undergoing HSCT are more prone to develop tuberculosis. The aim of our study was to evaluate prevalence of latent tuberculosis in HSCT recipients. In this study, 84 patients (2 months to 18 years) who were candidates for HSCT at the referral hospital of Tehran Children's Medical Center were enrolled. The TST and the QFT-GIT test were performed in all 84 patients, simultaneously. LTBI was considered when one of the tests was positive. Overall, the prevalence of LTBI in HSCT recipients in our study was 12% (10 cases). TST induration ≥5 mm was seen in only three patients (3.5%). Eight patients (9.5%) had a positive result for IGRA test, and 11 of them (13%) had indeterminate QFT-GIT result. The agreement between the TST results (induration size ≥5 mm) and the QFT-GIT results was poor (kappa = 0.14). In conclusion, there was a high rate of discordance between TST and IGRA results with many more positive QFT-GIT tests. However, more studies are needed in this population to determine whether this discordance reflects true infection.
Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): clinical, technical and socio-economic considerations
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.
Physical therapy pathway and protocol for patients undergoing hematopoietic stem cell transplantation: Recommendations from The Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) Group
Hematology/oncology and stem cell therapy. 2019
Patients undergoing hematopoietic stem cell transplantation (HSCT) are often referred for physical therapy (PT) to help improve their quality of life. However, to our knowledge there is no clear PT pathway to guide therapists and patients before, during, and after HSCT. This paper not only reviews the current evidence on safe PT practice but also puts forward a protocol and pathway for HSCT rehabilitation, highlights the importance of individualized exercise intervention for HSCT patients, and outlines safe practice guidelines for the physical therapists working in this field.
A Single-Center Experience With Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia: A Modest Pitch for Non-Total Body Irradiation Conditioning Regimens
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2018
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.
Challenges in managing graft-versus-host disease in developing countries: a perspective
Bone marrow transplantation. 2018
Hematopoietic cell transplant (HCT) activity is increasing worldwide due to safer techniques, widening indications, and more availability of donors. New HCT centers have recently been established in many developing countries including Asian and African countries. Due to limited resources, logistic, political, and social issues in developing countries, the treatment of orphan diseases like graft-versus-host disease (GVHD) can be challenging. We intended to delineate the current issues that institutions and clinicians face in managing GVHD. We conducted a comprehensive systematic electronic review of peer-reviewed published articles on GVHD management in developing countries. We used PubMed, Cochrane, and Embase databases as our primary source of data. Studies that were included described the treatments for both acute and chronic GVHD. Consensus on the use of high-dose methyl-prednisone and prednisolone as the initial therapy was widely accepted and used in practice. Socio-economic factors were found to be the major factor involved in GVHD management in lower income patients. Delayed diagnosis and treatment, lack of availability of healthcare professionals, lack of knowledge among cancer patients, and poverty are major concerns in the developing world. For optimal management, HCT programs should develop systems in place for long-term follow-up of HCT survivors and have a low threshold to initiate treatments for GVHD early. Awareness and health policy programs must be initiated at the grass-root level for long-term management of these survivors in developing countries.
Impact of hematopoietic stem cell transplant on VEP and ABR values of the patients with malignant infantile osteopetrosis
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2018
OBJECTIVES Malignant Infantile Osteopetrosis (MIOP) is a rare inherited disorder with neurological complications, notably visual impairment and decrease of hearing level. Although Hematopoietic Stem Cell Transplantation (HSCT) has been approved as the only curative treatment for these patients, the exact impact of it on visual and hearing level is still unclear. STUDY DESIGN We analyzed the P2 latency and amplitude from Visual Evoked Potentials (VEP) of 10 patients (20 eyes) and the threshold of wave V from Auditory Brainstem Response (ABR) of 15 patients (30 ears) with MIOP before, 6 and 12 months after HSCT. RESULTS Before the HSCT, 10/30 ears demonstrated some degree of hearing loss; while only 3/20 eyes had P2 wave latencies in normal range for age. Using GEE models, it was shown that 12 months after HSCT, wave V threshold of ABR of the patients was significantly lower compared to its value from before the transplant (p value: 0.04). The analysis of latency and amplitude of P2 wave of VEPs showed no significant difference between before and after the transplant. CONCLUSION This study clearly showed that HSCT can improve the hearing level of the patients in terms of ABR threshold. Although HSCT made no significant improvement in latency of P2 in VEP of the patients, it can be concluded that transplant can halt visual regression in these patients. Early diagnosis of MIOP with this objective tools and subsequently early HSCT in these patients can decrease the rate of neurological complications of MIOP and improve the quality of life in them.
Outcome Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Total Body Irradiation-Free Allogeneic Hematopoietic Stem Cell Transplantation: Comparison of Patients with and Without Central Nervous System Involvement
Biology of Blood & Marrow Transplantation. 2017
Hematopoietic stem cell transplantation (HSCT) with a non-total body irradiation (TBI) conditioning regimen has proven feasible for treating patients with acute lymphoblastic leukemia (ALL). However, it is commonly believed that for extramedullary involvement of ALL in sanctuary sites, such as the central nervous system (CNS), TBI shall not be abandoned. In this study, the outcomes of pediatric ALL patients with CNS involvement (CNS+) and without CNS involvement (CNS-) treated with TBI-free allogeneic HSCT were retrospectively compared. The patients received a TBI-free busulfan plus cyclophosphamide conditioning regimen. Comparing CNS+ (n=27) and CNS- (n=134) patients, the 5-year probabilities of relapse (44.4% versus 41.8%; P=.799), disease-free survival (DFS; 48.1% versus 43.3%; P=.642) and overall survival (OS; 51.9% versus 47.0%; P=.646) were not significantly different. Although transplantation-related mortality (TRM) was higher in the CNS- patients, the difference between the 2 groups was not significant (3.7% versus 12.7%; P=.177). In multivariate analysis, there were no significant between-group differences in OS (P=.502), DFS (P=.424), relapse rate (P=.226), or TRM (P=.117). These findings suggest that HSCT using a non-TBI-containing conditioning regimen can lead to similar outcomes in pediatric ALL patients with and without CNS involvement. TBI-free allogeneic HSCT might be feasible and effective for CNS+ ALL patients. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.