scholarly journals Investigating the Relationship between CD34+and CD3+ Cell Doses, One-Year Graft-Versus-Relapse-Free-Survival, Graft-Versus-Host Disease, and Overall Survival in Haploidentical Hematopoietic Stem Cell Transplantation Using Post Transplant Cytoxan: A Single Center Experience

2020 ◽  
Vol 26 (3) ◽  
pp. S289
Author(s):  
Mindy Hsiao ◽  
Anastasia Martynova ◽  
Chris Foss ◽  
George Yaghmour
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Single Center ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Graft Versus Host ◽  
Single Center Experience ◽  
One Year ◽  
The Relationship

scholarly journals Prognostic Factors on the Graft-versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yao-Chung Liu ◽  
Sheng-Hsuan Chien ◽  
Nai-Wen Fan ◽  
Ming-Hung Hu ◽  
Jyh-Pyng Gau ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematologic Malignancy ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Graft Versus Host ◽  
Disease Free

The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rankp<0.001). European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p<0.001) and hematologic malignancy (p=0.033) were poor prognostic factors for 1-year GRFS. For 2-year GRFS, EBMT risk score > 2 (p<0.001), being male (p=0.028), and hematologic malignancy (p=0.010) were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity.

scholarly journals Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome–Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study

2017 ◽  
Vol 35 (16) ◽  
pp. 1795-1802 ◽  
Author(s):  
Giovanni Martinelli ◽  
Nicolas Boissel ◽  
Patrice Chevallier ◽  
Oliver Ottmann ◽  
Nicola Gökbuget ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Response ◽  
Minimal Residual

Purpose Few therapeutic options are available for patients with Philadelphia chromosome–positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) −based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph+ ALL. Patients and Methods This open-label phase II study enrolled adults with Ph+ ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naïve responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph+ ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous experience in Ph– ALL.

Conditioning with 8 Gy Total Body Irradiation and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: Projected 4-Year Update.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3016-3016
Author(s):  
Matthias Stelljes ◽  
Martin Bornhaeuser ◽  
Matthias Kroger ◽  
Joerg Beyer ◽  
Maria C. Sauerland ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Dna Typing ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Unrelated Donors ◽  
Total Body ◽  
Acute Myeloid

Abstract Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase II study on reduced intensity myeloablative conditioning with fractionated 8 Gy total body irradiation (TBI) and fludarabine (120 mg/m2) (Blood. 2005 Nov 1;106(9):3314–21). Patients received mobilized peripheral blood stem cells (n=68) or bone marrow (n=3) from siblings (n=39) or unrelated donors (n=32). HLA-typing was performed for HLA-A, -B, -Cw (serological matching or intermediate resolution DNA typing), DRB1 and DQB1 (high resolution DNA typing). Three patients had unrelated donors with an allele mismatch in HLA DRB1 (2 with an additional mismatch in HLA Cw) and 7 patients were transplanted from unrelated donors with an antigen mismatch in HLA Cw. Thirty-six patients were transplanted in complete remission (CR) and 35 with untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20–66). Sustained engraftment was attained in all evaluable patients. With a median follow-up of now 41.3 months (range, 20.4–70.4) in surviving patients, probabilities of overall survival for patients transplanted in CR and non-CR were 80% (95% CI, 66 to 94%) and 17% (95% CI, 5 – 29%) at 4 years, respectively. Relapse-free survival rates were 57% (95% CI, 39 – 75%) and 14% (95% CI, 2 – 26%). Of the 35 evaluable patients transplanted in CR, 10 patients suffered a relapse between days 68 and 868 after transplantation (cumulative incidence 29%). Five patients with late relapse (>1 year after transplantation) achieved a subsequent CR after conventional chemotherapy, blood stem cell boost and treatment with granulocyte-macrophage colony-stimulating factor, lasting 2000+, 1841+, 909+, 847+ and 480 days, respectively. Depending on donor type, relapse-free survival was similar in patients transplanted from unrelated or sibling donors. Overall survival in patients transplanted in complete remission from unrelated vs. sibling donors was 84% (95% CI, 73 – 95%) vs. 77% (95% CI, 68 – 86%). The cumulative incidence of non-relapse mortality (NRM) in CR patients was 11% at 4 years and beyond (3 patients deceased before day 100 and 1 patient 25 months after transplantation), but amounted to 37% at 4 years in non-CR patients. Nine of the 33 surviving patients (27%) have actually active chronic GvHD (5 limited and 4 extensive disease). This update confirms that allogeneic HSCT from related or unrelated donors with 8 Gy TBI/fludarabine conditioning is feasible with low NRM and preserved long-term antileukemic activity in AML patients in first or later CR.

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.

Evaluation of Graft Versus Host Disease and Relapse Free Survival As Novel Endpoint in Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Joint Naples-Paris Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2285-2285
Author(s):  
Simona Pagliuca ◽  
Antonio M Risitano ◽  
Sylvie Chevret ◽  
Flore Sicre de Fontbrune ◽  
Alienor Xhaard ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Graft Versus Host

Abstract The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including acute and chronic graft-versus-host disease (GVHD), relapse and death. Classical endpoints such as overall survival (OS), desease free survival (DFS) and non relapse-mortality (NRM) had become more and more unsuitable for transplant research because of their inability to a dynamic mesure of transplant-associated comorbidity. For this reason several composite endpoints taking into account also GVHD-associated comorbidity were proposed in the last years. GVHD free/relapse free survival (GRFS), proposed by Holtan et al (Blood 2015), includes grades 3-4 acute GVHD, systemic therapy requiring chronic GVHD, primary disease relapse , or death for any cause considered as events. This endpoint seems to completely characterize the survival without mortality or ongoing morbidity. With the intent to analyse the outcomes of our transplanted cohort, we retrospectively analysed GRFS of 959 consecutive patients receiving HSCT at Federico II University in Naples (n=119) and Saint-Louis Hospital (n=840) in Paris between 2007 and 2014, identifying prognostic factors associated with a better outcome and estimating the incidences of all components of this endpoint: rates of acute and chronic GVHD, disease relapse and death. Patient, disease and transplant characteristics are listed in table 1. Median duration of follow-up after HSCT was 22.1 months (IQR: 5.6-51 months). Cumulative incidence at day 100 of grade II-IV acute GVHD and grade III-IV were 42% and 16%, respectively. Cumulative incidence of chronic GVHD requiring systemic treatment at 1 and 5 years was 23% and 33%, respectively, diagnosed according to NIH criteria [14% of patients had score 1 (mild), 58% score 2 (moderate) and 27% score 3 (severe)cGVHD]. Cumulative incidence of relapse (considering all malignant and non-malignant diseases) was 26.7% (N=219) at 5 years. Overall survival for the whole population was 57% (95%CI, 53.3-60.8) at 5 years and Disease free survival (DFS) and non-relapse mortality (NRM) were respectively 50% (95%CI, 46.6-53.8) and 23% at 5 years. GRFS was 25% (95%CI, 21.8-28.5) at 5 years. Factors identified as influencing GRFS based on univariate analyses were age higher than 45 years (HR=1.64, 95%CI, 1.40-1.92), bone marrow (BM) as stem cell source (HR=0.40, 95%CI, 0.32-0.50); reduced intensity conditioning (RIC) (HR=0.63, 95%CI, 0.53-0.74); disease type [non-malignant disorders: HR=0.24, 95%CI, 0.17-0.33; myelodysplastic and myeloproliferative syndromes (MPN/CML/MDS): HR=1.34, 95%CI, 1.10-1.63; whereas other diagnosis did not influence GRFS] and than unrelated donor (matched: HR=1.71, 95%CI, 1.41-2.07;mismatch:HR=1.81, 95%CI, 1.48-2.23). Based on a multivariable Cox model, only diagnoses (non-malignancies, HR=0.27, 95%CI, 0.19-0.38 and MPN/CML/MDS, HR= 1.35, 95%CI, 1.11-1.65), and HLA unrelated graft (matched, HR=1.42, 95%CI, 1.17-1.73 and mismatched, HR=1.55, 95%CI, 1.26-1.92) remained associated with the outcome (Figure 1 and 2). GRFS could represent the ideal endpoint following HSCT. It differs significantly based upon type of disease and donor type, essentially. This composite indicator yields more information regarding complications of HSCT than the simpler measurement of OS or DFS. Its use willbetter compare these clinically important outcomes that accompany disparate HSCT techniques. All examined prognostic factors could enhance our ability to optimally judge the risk and the probability of true recovery after allogeneic HSCT. Our data support the use of this composite endpoint to describe HSCT outcome, and also pave the way for the investigation of novel endpoints, which may also track the dynamic changes of post-transplant events in the long-term. These retrospective data represent the background to investigate the impact of novel strategies of HSCT aiming to improve the outcome of HSCT, as detectable, by using more sensitive endpoints, tracking clinical events associated with detrimental long-term outcome. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Risitano: Alexion Pharmaceuticals: Other: lecture fees, Research Funding; Novartis: Research Funding; Alnylam: Research Funding; Rapharma: Research Funding. Peffault de Latour:Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding.

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