scholarly journals The Impact of HLA Mismatch Direction on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in AML Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4608-4608
Author(s):  
Wen-Chun Chen ◽  
Jyh-Pyng Gau ◽  
Liang-Tsai Hsiao ◽  
Chia-Jen Liu ◽  
Yao-Chung LIU ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Matched Group ◽  
The Impact

Background: For patients with acute myeloid leukemia (AML) who were classified as high risks, failed to achieve complete remission, or relapsed disease after remissions, allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers the chance of durable remission and the potential to cure. In the absence of 8/8 matched donors, an HLA 1-allele mismatched (7/8 1-MM) unrelated donor is an alternative source of hematopoietic stem cell. However, the impact of HLA homozygosity at 1-MM on the outcome and the consensus at desirable donor screening in 7/8 HLA mismatched is not yet clear. A 1-MM in the host-versus-graft (HVG) direction is a 7/8 unidirectional mismatch for a homozygous recipient receiving a graft from a heterozygous donor. A 1-MM in the graft-versus-host (GVH) is for a heterozygous recipient receiving a graft from a homozygous donor. 7/8 bidirectional mismatch is a heterozygous recipient receiving a graft from heterozygous donor. From the biological perceptions, the impact of different histocompatibility transplantations may differ on the prognosis. This study evaluated the outcome of unidirectional and bidirectional 7/8 mismatches in recipients receiving either bone marrow or peripheral blood hematopoietic stem cell for AML patients. Methods: Patients who were at least 12 years of age with AML receiving first hematopoietic stem cell transplantation from a serologically HLA-A, -B, -C, and -DR allele data were included in our study between 2009 and 2014. Data were obtained from Taiwan Society of Blood and Marrow Transplantation (TBMT) Research Database. We excluded those who received HLA-matched sibling grafts, HLA-haploidentical grafts, or unrelated donors who had more than 1-allele mismatch. Those who lacked the clinical information on survival status or survival date were also eliminated. Patients were divided into four histocompatibility groups based on typing at HLA-A, -B, -C, and -DR as unidirectional 7/8 HVG, unidirectional 7/8 GVH, bidirectional 7/8, and 8/8 matched group. Descriptive statistics were used to describe the patients' characteristics, disease status on the time receiving HSCT, intensity of conditioning regimen and treatment features. Associations between four groups and outcomes of overall survival, relapse-free survival, acute GVHD, chronic GVHD, treatment-related mortality (TRM), relapse rate, neutrophil engraftment, engraftment syndrome, and engraftment failures were reviewed. Results: A total of 222 recipients of all-HSCT were included in the analysis. The four comparison groups included nine patients designated as 1-MM HVG, nine as 1-MM GVH, 71 as 1-MM bidirectional, and 133 as 8/8 matched group. Table 1 shows patient and transplant characteristics. Superior overall survival was significantly associated with the higher intensity of induction regimen (myeloablative conditioning, MAC and reduced intensity conditioning, RIC, p<0.05) and the disease status on the time receiving allo-HSCT (p=0.1). Relapse-free survival was significantly decreased with RIC regimen (p < 0.05, figure 1). The cumulative 5-year overall survival rate was 75% in the 1-MM HVG group, 50% in the 1-MM GVH group, 50% in the 1-MM bidirectional group, and 44% in the 8/8 matched group. Median survival of 1-MM HVG and 8/8 matched group didn't reach under analysis, and which is 62.2 months in 1-MM GVH, 30.9 months in 1-MM bidirectional group. The outcome of overall survival was more favorable in the 1-MM HVG group (Figure 2 and Figure 3), especially comparing with 1-MM bidirectional group (p=0.07), where there was no significant difference between 8/8-matched group and 1-MM GVH group or the 1-MM bidirectional group. Superior overall survival and relapse free survival was observed in 1-MM HVG group, although the differences were not statistically significant. Hyper-acute GVHD was slightly higher in 7/8 bidirectional group, while no significant difference was observed in acute and chronic GVHD among four groups. The primary causes of death were reviewed. 8/8 matched group had higher deaths attributed to disease relapse (26.3%), while 1-MM GVH group had more deaths attributed to GVHD (22.2%). Conclusion: Myeloabltive conditioning regimen is associated with more favorable outcomes of overall survival and relapse free survival. 1-MM HVG also tends to have superior overall survival and relapse free survival, although there is no statistical significance due to limited cases. Disclosures No relevant conflicts of interest to declare.

Current IST-free/relapse-free survival as a new endpoint after allogeneic hematopoietic stem cell transplantation

2020 ◽  
Vol 99 (5) ◽  
pp. 1149-1150
Author(s):  
Roberto Crocchiolo ◽  
Alessio Signori ◽  
Mohamad Sobh ◽  
Helene Labussiere ◽  
Myriam Renault ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival

scholarly journals Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT

Leukemia ◽  
2021 ◽  
Author(s):  
Nicolaus Kröger ◽  
Giulia Sbianchi ◽  
Tiarlan Sirait ◽  
Christine Wolschke ◽  
Dietrich Beelen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Significant Difference ◽  
Pretreated Patients ◽  
The Impact

AbstractJAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n = 274) or with (n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p = 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p = 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p = 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age > 58 years (p = 0.03) and HLA mismatch donor (p = 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

scholarly journals Anti-Thymocyte Globulin Prophylaxis in Patients With Hematological Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: An Updated Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xue Yang ◽  
Dongjun Li ◽  
Yao Xie
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Meta Analysis ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Barr Virus

BackgroundAnti-thymocyte globulin (ATG) prophylaxis reduces graft-versus-host disease (GVHD) incidence. This meta-analysis aimed to explore the long-term efficacy of ATG and the influencing factors in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsPubMed, Embase, and Cochrane databases were searched for the relevant studies published up to August 2020. Data from randomized controlled trials (RCTs) on ATG prophylaxis for GVHD prevention in allo-HSCT patients were extracted.ResultsA total of eight relevant RCTs (1,348 patients) were included. ATG significantly reduced the incidence of grade III–IV aGVHD (P = 0.001) and cGVHD (P &lt; 0.001). ATG significantly improved the GVHD relapse-free survival (GRFS) (P &lt; 0.001). The immunosuppressive regimen (number and dose of immunosuppressants) was significantly reduced when using ATG (P = 0.005). Epstein-Barr virus (EBV) reactivation was high in patients receiving ATG (P = 0.003). No significant differences were detected in relapses, overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) between the ATG and no ATG groups. Subgroup analyses revealed that the donor type and ATG formulation might be the possible sources of heterogeneity among the included studies. Meta-regression analysis showed that the cumulative dose of ATG did not affect GVHD, OS, relapse, RFS, and NRM.ConclusionAlthough ATG had no significant effect on relapse, RFS, and NRM, it significantly reduced the occurrence and severity of GVHD, improved the GRFS, and reduced the number and dose of immunosuppressants in patients undergoing allo-HSCT.

scholarly journals The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children—A Single Center Experience

2021 ◽  
Vol 10 (5) ◽  
pp. 1113
Author(s):  
Kinga Musiał ◽  
Krzysztof Kałwak ◽  
Danuta Zwolińska
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Serum Creatinine ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Kidney Function ◽  
Hematopoietic Stem ◽  
Oncological Patients ◽  
The Impact

Background: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. Objectives: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. Materials and Methods: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. Results: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2–3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. Conclusions: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.

The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2003-2008 ◽  
Author(s):  
Michael Boeckh ◽  
W. Garrett Nichols
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cohort Studies ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Preemptive Therapy ◽  
Prevention Strategies ◽  
Hematopoietic Stem ◽  
The Impact

AbstractIn the current era of effective prophylactic and preemptive therapy, cytomegalovirus (CMV) is now a rare cause of early mortality after hematopoietic stem cell transplantation (HSCT). However, the ultimate goal of completely eliminating the impact of CMV on survival remains elusive. Although the direct effects of CMV (ie, CMV pneumonia) have been largely eliminated, several recent cohort studies show that CMV-seropositive transplant recipients and seronegative recipients of a positive graft appear to have a persistent mortality disadvantage when compared with seronegative recipients with a seronegative donor. Recipients of T-cell–depleted allografts and/or transplants from unrelated or HLA-mismatched donors seem to be predominantly affected. Reasons likely include both incomplete prevention of direct and indirect or immunomodulatory effects of CMV as well as consequences of drug toxicities. The effect of donor CMV serostatus on outcome remains controversial. Large multicenter cohort studies are needed to better define the subgroups of seropositive patients that may benefit from intensified prevention strategies and to define the impact of CMV donor serostatus in the era of high-resolution HLA matching. Prevention strategies may require targeting both the direct and indirect effects of CMV infection by immunologic or antiviral drug strategies.

scholarly journals Induction Treatment and Feasibility of Allogeneic Hematopoietic Stem Cell Transplantation in Young Patients (<65 years) with High-Risk Cytogenetic and Secondary Acute Myeloid Leukemia (AML): A Single Center Experience in Argentina with CLAG-M and 7+3

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5132-5132
Author(s):  
Maria Lucia Fuente ◽  
Maria Del Rosario Custidiano ◽  
Santiago Cranco ◽  
Laura Korin ◽  
Paola Ochoa ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Median Time ◽  
Induction Treatment ◽  
Hematopoietic Stem ◽  
Free Survival

BACKGROUND Patients with adverse cytogenetic or secondary AML (s-AML) have significantly worse outcomes and lower survival rates. In this high risk subgroup of patients, early consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) can improve results, especially in those who achieve negative measurable residual disease (MRD-). More effective treatments than standard 7+3 are needed. CLAG-M is a salvage regimen that has demonstrated high response rates with good tolerance, and seems to be promising in the upfront setting. AIMS To estimate CR and MRD- rates, overall survival (OS) and event free survival (EFS) in transplant eligible patients with high risk AML treated in our center.To compare CR rate and transplant feasibility in CR1 with 7+3 vs. CLAG-M as induction treatment in s-AML. PATIENTS AND METHODS We analyzed adult patients (18-65 years old) with high risk AML (defined by adverse cytogenetic according to ELN2017 or s-AML) who were treated in our institution between 2010 and 2018. All patients were transplant eligible and had an available donor. Clinical information was collected from medical records. We evaluated CR1 and MRD- rates, EFS and OS. We also compared CR rates and HSCT feasibility in s-AML after treatment induction with CLAG-M and 7+3. The survival analysis was estimated with Kaplan-Meier method and the comparison between variables was performed through log-rank test. RESULTS Twenty-one patients were included (13 s-AML and 8 with adverse cytogenetic). The median age at diagnosis was 54 years (21-64); 13 female/8 male. Out of 21 patients, 14 received 7+3 induction and 7 CLAG-M. The median follow-up time was 11 months (0.9-90.8), median EFS and OS for the whole group was 1.05 and 13.5 months, respectively. Two-year OS was 35%. CR1 was achieved in sixteen patients (76%), 10 of them MRD-. The median time to CR1 was 33 days, the median OS of these patients was 26.7 months (figure 1). Eleven patients (52%) were refractory to first induction, 10/14 in the 7+3 subgroup, and only 1/7 patients treated with CLAG-M. Six of them converted to CR after reinduction (5 with CLAG-M). Fourteen (67%) underwent HSCT in CR1. The median time to HSCT consolidation was 106 days. The median relapse free survival in transplanted patients has not been reached (Table 1). Considering only s-AML, 6 patients received 7+3 and 7 CLAG-M. Median age in 7+3 subgroup was 41 vs. 57 years in CLAG-M. The median OS was 13.5 months. In the 7+3 cohort, only 1 achieved CR (16%); the other five received reinduction with CLAG-M, and 4 converted to CR1. The median time to CR1, EFS and OS were 82 days, 1 month and 26 months respectively. In contrast, 4 of the 7 patients (57%) that received CLAG-M achieved CR1, but only 1 of the 3 that were refractory could convert to CR. The median time to CR1 in patients treated with CLAG-M was 27 days, median EFS 7.5 months and median OS has not been reached (Figure 2). There were no statistically significant differences between the two treatment groups. Eight patients (62%) could be bridged to HSCT, 4 of each subgroup (Table 2). CONCLUSIONS Our results in this real life small cohort of high risk AML were similar to historical controls. In the s-AML subgroup, differences between 7+3 and CLAG-M were not statistically significant probably due to the low number of patients analyzed. However, patients who received CLAG-M required less cycles of treatment to achieved CR1, allowing HSCT rapidly in this selected population. Since most of the refractory patients to 7+3 responded to reinduction with CLAG-M, both groups had similar transplant rates. According to our experience CLAG-M might be an attractive treatment option with high CR rates and acceptable safety profile. In this high risk AML population, two thirds of the patients were effectively "bridged" to HSCT with a 2-year OS rate of 35%. Disclosures No relevant conflicts of interest to declare.

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