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Frontiers in Oncology 2024The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute...
BACKGROUND
The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified.
OBJECTIVE
The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD.
STUDY DESIGN
We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD.
RESULTS
Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS ( = 0.009) and overall survival (OS) ( = 0.070) due to lower CIR ( = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status.
CONCLUSIONS
Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.
PubMed: 38756667
DOI: 10.3389/fonc.2024.1394648 -
Cancer Medicine May 2024Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities...
INTRODUCTION
Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post-transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution.
METHODS
Treosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non-relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed.
RESULTS
The median follow-up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non-relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962).
CONCLUSION
Treosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan.
Topics: Humans; Busulfan; Transplantation Conditioning; Female; Male; Hematopoietic Stem Cell Transplantation; Adult; Middle Aged; Graft vs Host Disease; Retrospective Studies; Young Adult; Transplantation, Homologous; Adolescent; Treatment Outcome; Aged; Antineoplastic Agents, Alkylating
PubMed: 38752476
DOI: 10.1002/cam4.7292 -
Swiss Medical Weekly May 2024Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was...
AIM
Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development.
METHODS
All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years.
RESULTS
Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death.
CONCLUSION
Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Switzerland; Male; Female; Adult; Middle Aged; Transplantation, Homologous; Protein Kinase Inhibitors; Adolescent; Transplantation Conditioning
PubMed: 38749067
DOI: 10.57187/s.3754 -
BMC Pediatrics May 2024The risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic review and meta-analysis to investigate the risk factors for HC in children undergoing HSCT.
METHODS
We performed this meta-analysis by retrieving studies from PubMed, EMBASE, and the Cochrane Library up to October 10, 2023, and analyzing those that met the inclusion criteria. I statistics were used to evaluate heterogeneity.
RESULTS
Twelve studies, including 2,764 patients, were analyzed. Male sex (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.16-2.00; p = 0.003, I = 0%), allogeneic donor (OR = 5.28; 95% CI, 2.60-10.74; p < 0.00001, I = 0%), human leukocyte antigen (HLA) mismatched donor (OR = 1.86; 95% CI, 1.00-3.44; p = 0.05, I = 31%), unrelated donor (OR = 1.58; 95% CI, 1.10-2.28; p = 0.01, I = 1%), myeloablative conditioning (MAC) (OR = 3.17; 95% CI, 1.26-7.97; p = 0.01, I = 0%), busulfan (OR = 2.18; 95% CI, 1.33-3.58; p = 0.002, I = 0%) or anti-thymoglobulin (OR = 1.65; 95% CI, 1.07-2.54; p = 0.02, I = 16%) use, and cytomegalovirus (CMV) reactivation (OR = 2.64; 95% CI, 1.44-4.82; p = 0.002, I = 0%) were risk factors for HC in children undergoing HSCT.
CONCLUSIONS
Male sex, allogeneic donor, HLA-mismatched, unrelated donor, MAC, use of busulfan or anti-thymoglobulin, and CMV reactivation are risk factors for HC in children undergoing HSCT.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Cystitis; Risk Factors; Child; Hemorrhage; Transplantation Conditioning; Sex Factors; Male; Female; Cystitis, Hemorrhagic
PubMed: 38745164
DOI: 10.1186/s12887-024-04815-x -
Cureus Apr 2024Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for sickle cell anaemia (SCA). While HSCT offers the possibility of disease...
BACKGROUND
Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for sickle cell anaemia (SCA). While HSCT offers the possibility of disease remission, it can also lead to long-term complications, including gonadal dysfunction and premature menopause.
METHODS
We conducted a retrospective cohort study of female survivors who had hydroxyurea therapy and those who underwent post-HSCT follow-up for SCA at a teaching hospital in Lagos, Nigeria, between January 2019 and December 2022. Participants were eligible if they were at least five years post-HSCT or hydroxyurea treatment and had available serum samples for markers of ovarian function measurement. Demographic and clinical data were collected from the hospital register and patients' medical records. Serum levels of oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) were measured using the Abbott Architect i1000SR chemiluminescent immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL). Descriptive statistics and inferential analyses were used to assess the relationship between markers of ovarian function (FSH and AMH) and clinical parameters.
RESULTS
There were statistically significant differences in the median serum levels of all the assessed endocrine hormones between the HSCT and non-HSCT (hydroxyurea) groups of SCA survivors. Up to 82.6% of the SCA survivors experienced ovarian dysfunction after HSCT treatment. Impaired ovarian function in SCA survivors was associated with a longer median follow-up duration than in SCA survivors who had normal ovarian function (12.0 vs. 7.5 years, p = 0.048). There were higher odds of impaired ovarian function in the SCA survivors who had myeloablative regimens than in those who had reduced intensity conditioning regimens (94.1% vs. 50.0%, p = 0.040).
CONCLUSION
Our study highlights the significant impact of HSCT on long-term ovarian function in female SCA survivors. However, further prospective studies with larger sample sizes and longer follow-up periods are required to confirm our findings and elucidate the factors influencing ovarian function in SCA survivors of HSCT. In addition, studies are also needed to further elucidate the optimal transplant protocols and fertility preservation strategies to minimize gonadal toxicity and preserve reproductive potential in female SCA patients undergoing HSCT.
PubMed: 38741860
DOI: 10.7759/cureus.58195 -
Cryobiology May 2024Increasing shortage of donor organs leads to the acceptance of less than optimal grafts for transplantation, up to and including organs donated after circulatory...
Increasing shortage of donor organs leads to the acceptance of less than optimal grafts for transplantation, up to and including organs donated after circulatory standstill of the donor. Therefore, protective strategies and pharmacological interventions destined to reduce ischemia induced tissue injury are considered a worthwhile focus of research. The present study evaluates the potential of a multidrug pharmacological approach as single flush at the end of static preservation to protect the liver from reperfusion injury. Livers were retrieved from male Wistar rats 20 min after cardiac standstill. The organs were cold stored for 18 h, flushed with 20 ml of saline, kept at room temperature for 20 min, and reperfused at 37 °C with oxygenated Williams E solution. In half of the cases, the flush solution was supplemented with a cocktail containing metformin, bucladesine and cyclosporin A. Upon reperfusion, treated livers disclosed a massive mitigation of hepatic release of alanine aminotransferase and aspartate aminotransferase, along with a significant approximately 50 % reduction of radical mediated lipid peroxidation, caspase activation and release of TNF-alpha. Even after preceding cold preservation, a pharmacological cocktail given as single flush is capable to mitigate manifestations of reperfusion injury in the present model.
PubMed: 38734364
DOI: 10.1016/j.cryobiol.2024.104904 -
Transplantation Proceedings May 2024Hematopoietic stem cell transplants (HSCT) treat malignant and nonmalignant diseases. Aplastic anemia (AA) is a rare condition associated with ineffective hematopoiesis....
BACKGROUND
Hematopoietic stem cell transplants (HSCT) treat malignant and nonmalignant diseases. Aplastic anemia (AA) is a rare condition associated with ineffective hematopoiesis. The first-line treatment for AA is an allogenic hemopoietic stem cell transplant (allo-HSCT). After allo-HSCT, most patients become infertile.
METHODS
This study presents 2 case reports of women who become pregnant after allo-HSCT in the treatment of severe AA. In both women, conditioning was performed using the fludarabine, cyclophosphamide, and antithyroglobulin antibodies protocol.
RESULTS
Case 1, a 27-year-old woman, underwent allo-HSCT at the age of 19. She received cyclosporine immunosuppression. The transplant was without complications. The woman's menstrual resumption was observed after 2 months. Eight years post-transplantation, the woman had her first pregnancy. Fetal growth restriction was diagnosed, and she was qualified for labor induction after the 37th week of gestation. She gave birth to a baby boy in good general condition. Case 2 is a 28-year-old woman with allo-HSCT at aged 25. The procedure was performed during a period of active fungal infection. Immunosuppression with cyclosporine and methotrexate was administered. During the transplant procedure, she developed acute kidney injury and liver failure. Her menstrual cycle returned 1 month after the transplant. Three years after the transplant, the woman was pregnant with twins. After 37 weeks of gestation, the woman was qualified for Cesarean delivery. Both babies, a boy and a girl, were in good general condition.
CONCLUSION
Preservation of fertility after allo-HSCT is feasible, particularly in those with AA treated with conditioning regimens without total body irradiation with lower doses of alkylating agents.
PubMed: 38729833
DOI: 10.1016/j.transproceed.2024.04.001 -
Cells Apr 2024Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been... (Review)
Review
Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25-57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.
Topics: Humans; Leukemia, Myeloid, Acute; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease
PubMed: 38727291
DOI: 10.3390/cells13090755 -
Cancer Research and Treatment May 2024Numerous patients experience long-term complications after HSCT. This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications...
PURPOSE
Numerous patients experience long-term complications after HSCT. This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses.
MATERIALS AND METHODS
We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases-10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis.
RESULTS
A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, TBI-based conditioning regimen, and non-Antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus.
CONCLUSION
The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.
PubMed: 38726507
DOI: 10.4143/crt.2024.047 -
Frontiers in Immunology 2024For children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients... (Comparative Study)
Comparative Study
Comparison of upfront haploidentical hematopoietic stem cell transplantation and salvage haploidentical hematopoietic stem cell transplantation after immunosuppressive therapy in children with acquired severe aplastic anemia - a multicenter study.
BACKGROUND
For children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients without matched sibling donor (MSD) and matched unrelated donor (MUD), haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) can be chosen as a salvage treatment. This article aims to explore the comparison between upfront Haplo-HSCT and salvage Haplo-HSCT after IST.
METHODS
29 patients received salvage Haplo-HSCT, and 50 patients received upfront Haplo-HSCT. The two groups received Bu (Busulfan, 3.2mg/kg/d*2d on days -9 to-8), CY (Cyclophosphamide, 60mg/kg/d*2d on days -4 to-3), Flu (fludarabine, 40mg/m/d*5d on days -9 to -5) and rabbit ATG (Anti-thymocyte globulin, total dose 10mg/kg divided into days -4 to -2).
RESULTS
The OS of the salvage Haplo-HSCT group showed no difference to the upfront Haplo-HSCT group (80.2 ± 8.0% vs. 88.7 ± 4.8%, p=0.37). The FFS of the salvage Haplo-HSCT group also showed no difference to the frontline Haplo-HSCT group (75 ± 8.2% vs. 84.9 ± 5.3%, p=0.27). There was no significant difference in the incidence of other complications after transplantation between the two groups, except for thrombotic microangiopathy (TMA). In the grouping analysis by graft source, the incidence of II-IV aGVHD in patients using PBSC ± BM+UCB was lower than that in the PBSC ± BM group (p=0.010).
CONCLUSION
Upfront Haplo-HSCT and salvage Haplo-HSCT after IST in children with acquired severe aplastic anemia have similar survival outcomes. However, the risk of TMA increases after salvage Haplo-HSCT. This article provides some reference value for the treatment selection of patients. In addition, co-transplantation of umbilical cord blood may reduce the incidence of GVHD.
Topics: Humans; Anemia, Aplastic; Hematopoietic Stem Cell Transplantation; Male; Female; Child; Child, Preschool; Transplantation, Haploidentical; Salvage Therapy; Adolescent; Graft vs Host Disease; Immunosuppressive Agents; Transplantation Conditioning; Infant; Treatment Outcome; Immunosuppression Therapy
PubMed: 38720904
DOI: 10.3389/fimmu.2024.1384640