Soluble BAFF Is Elevated Following Allogeneic SCT but Is Not an Early Predictor for the Development of cGVHD.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 167-167 ◽  
Author(s):  
John D. Dickinson ◽  
Iskra Pusic ◽  
Christoph Rader ◽  
Seth Steinberg ◽  
Fran Hakim ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cells ◽  
De Novo ◽  
Chronic Gvhd ◽  
Multiple Time ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Time Points ◽  
Onset Type ◽  
Normal Plasma

Abstract Chronic GVHD (cGVHD) is a significant complication following hematopoietic stem cell transplantation (SCT). Yet much remains uncertain regarding the molecular pathogenesis of cGVHD. There is growing evidence that B cells play a role in cGHVD. BAFF is a member of the TNF family, expressed by myeloid cells, that promotes survival and differentiation of mature B cells. Soluble BAFF has been associated with a number of autoimmune diseases and may also play a role in alloimmune diseases such as chronic GVHD. The role of BAFF expression in the context of immune reconstitution, and allogeneic GVL/GVHD is not yet understood. In this study we measured plasma BAFF levels by ELISA at multiple time points following SCT in 63 leukemia/lymphoma patients. Samples were collected at time of enrollment in the NCI cGVHD Natural History Protocol. Of the 50 patients who developed cGVHD, 24 patients had progressive onset type, 6 had quiescent type onset, and 20 had de novo onset type cGVHD. Forty-nine of these cGVHD cases were classified as extensive under the Seattle Classification. BAFF expression was not significantly different in terms of cGVHD onset type (de novo vs. other) (p=0.32) but there was a significant correlation of BAFF with naïve CD19+IgD+CD27- cells (p=0.011), and a negative correlation with memory CD19+IgD-CD27+ cells (p=0.019) by Spearman Correlation. BAFF expression was then compared among those with cGVHD (n=50), those without a clinical history of cGVHD (n=13), normal plasma donors (n=11), and post autologous stem cell transplant breast cancer patients (n=9). Plasma BAFF level was significantly higher in the group with cGVHD (median 2723 pg/mL) compared to normal plasma donors (median 119 pg/mL, p<0.001) and autologous SCT patients (1311 pg/mL, p=0.033). BAFF expression was not significantly different from those post-allotransplant patients without evidence of clinical cGVHD (median 1160 pg/mL, p=0.277). BAFF expression was followed in a longitudinal fashion at the end of conditioning prior to SCT and then at 3, 6, 9, 12, and 18 months. In all cases, BAFF levels were highest at time of conditioning and subsequently declined. There was no major difference over time in BAFF expression between those who developed or did not develop cGVHD. Autologous SCT demonstrated a more precipitous decline in BAFF expression. Finally, plasma BAFF expression was analyzed as a predictor for the development of cGVHD. BAFF was measured at the end of conditioning prior to SCT and at 3 months post transplant in 22 allogeneic SCT patients. There was no significant correlation in the development of clinical cGVHD according to the level of BAFF at either of these time points by log rank analysis, p=0.38 and p=0.53 respectively. In conclusion, BAFF was found at higher levels in allogeneic SCT patients relative to normal donors or autologous SCT patients. While at a higher level, there was no statistical difference in BAFF levels between allogeneic SCT patients with or without clinical cGVHD. Elevated BAFF reflects the allogeneic reaction and it’s expression extends beyond engraftment and G-CSF period. It is less specifically associated with clinical cGVHD. It remains uncertain whether BAFF is a suitable target for therapy that decreases cGVHD and preserves GVL.

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

scholarly journals Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lorenzo Canti ◽  
Stéphanie Humblet-Baron ◽  
Isabelle Desombere ◽  
Julika Neumann ◽  
Pieter Pannus ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Chronic Gvhd ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Factors Affecting

Abstract Background Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. Methods Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses. Results Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01). Conclusions Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination. Trial registration The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).

Tandem Autologous Stem Cell Transplants (auto-auto) with or without Maintenance Therapy Versus Single Autologous Transplant Followed by HLA-Matched Sibling Non- Myeloablative Allogeneic Stem Cell Transplant (auto-allo) for Patients (pts) with High Risk (HR) Multiple Myeloma (MM): Results From the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0102 Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 526-526 ◽  
Author(s):  
Edward A Stadtmauer ◽  
Amrita Krishnan ◽  
Marcelo C Pasquini ◽  
Marian Ewell ◽  
Edwin P Alyea ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Cell Transplant ◽  
Primary Analysis ◽  
Hematopoietic Stem

Abstract Abstract 526 The prognosis of patients with high-risk myeloma (HR MM) continues to be dismal, despite the early incorporation of novel agents. Early phase trials of allogeneic hematopoietic stem cell transplant (alloHCT) suggest the possibility of an immunologic graft-versus-myeloma effect that might favorably affect survival. Less toxic reduced-intensity HCT preparative regimens now allow more widespread use of alloHCT in the MM population. BMT CTN 0102 is a phase III multicenter clinical trial that biologically assigned patients to either melphalan 200mg/m2 (MEL 200) auto-auto without (obs) or with 1 year of thalidomide and dexamethosone (ThalDex), or an auto-allo approach using MEL 200 followed by alloHCT using 2 Gy total body irradiation. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine and mycophenolate mofetil. Patients were stratified by biological prognostic factors that were considered to be high risk at the time of the trial design: chromosome 13 deletions by metaphase karyotype and beta-2 microglobulin ≥4 mg/dl. The primary endpoint was 3-year progression free survival (PFS). Between December 2003 and March 2007, 710 patients from 43 US centers were enrolled, and 85 fulfilled the criteria of HR MM. Among them, 48 were assigned to auto-auto (24 Thal-Dex and 24 obs) and 37 to auto-allo. Groups differed in age (median 57 y and 51y, p=0.02) but were otherwise balanced. Compliance with second transplant was 65% for auto-auto and 78% for auto-allo. Compliance with ThalDex was poor, so the two auto-auto arms were pooled for the primary analysis. Three-year PFS was 33% (95% Confidence Interval (CI), 22–50%) and 40% (95% CI, 27–60%, p=0.74) and 3-year OS was 67% (95% CI, 54–82%) and 59% (95% CI, 49–78%, p=0.46) for auto-auto and auto-allo, respectively. Corresponding probabilities for 3-year progression/relapse was 53% and 33% (p=0.09), and 3 year treatment-related mortality was 8% and 20% (p=0.3). Among auto-allo patients, probabilities of grade 3–4 acute and chronic GVHD were 9% and 48%, respectively. Among the 59 (31 auto-auto, 28 auto-allo) patients who received second transplant, 3 year PFS was 35% and 46% (p=0.6). Disease response at day 56 after second transplant was 57% for very good partial response (VGPR) or better and 37% for complete response (CR) and near CR (nCR) in the auto-auto group; and 48% (VGPR or better) and 41% (CR+nCR) in the auto-allo group. In conclusion, this planned secondary analysis of a cohort of HR MM patients demonstrated equivalent 3-year PFS and OS for auto-auto and auto-allo in both intention-to-treat and as-treated analyses. However, trends in late PFS and time to progression/relapse suggest further follow-up is needed before final conclusions regarding the utility of auto-allo in this HR cohort can be made. Finally, this study shows the feasibility of an alloHCT approach for HR MM patients and may serve as a platform for future studies seeking to enhance graft-versus-myeloma effects. Disclosures: Stadtmauer: Celgene: Speakers Bureau. Krishnan:Celgene: Speakers Bureau. Qazilbash:Celgene: Speakers Bureau. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

A Novel Chemotherapy-Based Allogeneic Hematopoietic Stem Cell Transplant Regimen for Very Young Children with Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3149-3149
Author(s):  
Susan E. Prockop ◽  
Nancy A. Kernan ◽  
Elizabeth G Klein ◽  
Rachel Kobos ◽  
Andromachi Scaradavou ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Young Children ◽  
Cord Blood ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant

Abstract Abstract 3149 Young children in need of allogeneic hematopoietic stem cell transplant (HSCT) are at increased risk of unacceptable side effects from total body irradiation (TBI) and have historically been considered candidates for non-TBI containing regimens. However, disease free survival (DFS) has been poorer in cohorts of very young patients transplanted without TBI and novel chemotherapy based regimens are needed. We report results in a cohort of 14 children all under three years of age at the time of transplant (6 – 32 months; median 19.8 months) using a clofarabine-based ablative regimen. Fourteen patients in this age group have undergone transplant with a regimen consisting of clofarabine 20 mg/m2/day × 5, thiotepa 10 mg/Kg/day × 1 and melphalan 70 mg/m2/day × 2. All patients had high risk disease. Seven (7) pts were transplanted for ALL, 6 for AML and 1 for JMML. Patients with ALL or AML in first remission (CR1) or CR2, were categorized as patients with good risk disease while all other pts were considered as poor risk irrespective of all other factors. Transplant risk was good for 6/7 with ALL, and 3/6 with AML. The patient with JMML had stable disease. Stem cell grafts consisted of unmodified bone marrow (BMT) (N=6), double cord blood (dCBT) (N=7) and T cell depleted PBSCT (N=1). Donors were matched unrelated (N=5) or mismatched unrelated (N=9) including 7 double umbilical cord blood grafts, and one T cell depleted graft. Graft versus host disease (GvHD) prophylaxis was with tacrolimus and methotrexate for unmodified BMT, tacrolimus and mycophenolate for dCBT or T cell depleted HSCT. Two patients died early post transplant of infection (1) and acute GvHD (1). Neutrophil engraftment for the 13 evaluable patients was at a median of 13 days (10 –29 days) for PBSC and BM grafts and 17.5 days (12 –23 days) for recipients of CB grafts. Platelet engraftment for the 12 evaluable patients was at a median of 23 days (16 – 36 days) for recipients of PBSC and BM grafts and 43.5 days (36 –66 days) for recipients of CB grafts. In all five patients developed grade II-IV GvHD, and two patients chronic GvHD. Seven patients developed transaminitis which resolved in all cases. No patients developed Grade IV mucositis. One patient (AML) died after relapsing 5.5 months post transplant. Two patients are alive after relapsing at 1.3 months (AML) and 10.8 months (JMML) post-transplant. Nine of the 14 patients are alive in continuous complete remission seven of whom are greater than 36 months from transplant (40.2 – 71 months). The seven patients without chronic GvHD have had robust immune reconstitution, have responded to vaccination, and continue to meet growth and developmental milestones. Only one patient (transplanted at 14 months of age) has mild neurocognitive deficits. This novel chemotherapy based regimen is associated with durable engraftment of unmodified and cord blood HSCT grafts and promising disease free survival in very young children with leukemia. Based on the low toxicity profile in this cohort of patients higher dosing of clofarabine will be explored as a possible way to improve leukemia remission in the highest risk patients. Disclosures: Off Label Use: Clofarabine.

Hematopoietic stem cell dose correlates with the speed of immune reconstitution after stem cell transplantation

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4344-4352 ◽  
Author(s):  
Benny J. Chen ◽  
Xiuyu Cui ◽  
Gregory D. Sempowski ◽  
Jos Domen ◽  
Nelson J. Chao
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
B Cells ◽  
Hematopoietic Stem Cells ◽  
Immune Reconstitution ◽  
Hematopoietic Stem ◽  
Time Points ◽  
Cell Dose

Abstract In the current study, we tested whether higher numbers of hematopoietic stem cells correlate with the speed of immune reconstitution in a congenic transplantation model (C57BL/Ka, CD45.1, Thy1.1→C57BL/6, CD45.2, Thy1.2) using purified hematopoietic stem cells (c-Kit+Thy1.1lowLin-/lowSca-1+). There were 3 different doses of stem cells used (400, 1000, and 5000). Phenotypic analyses in peripheral blood and spleen demonstrated that higher numbers of infused stem cells are associated with more rapid regeneration of T cells (CD4+, CD8+, naive CD4+, naive CD8+) and B cells at early time points. The numbers of T and B cells eventually became equivalent between different dose groups at late time points. Production of interleukin-2 and inter-feron-γ per T cell was similar regardless of stem cell dose even when tested at the time when there were significant differences in peripheral T-cell counts. The improved immune recovery was attributed to a more rapid regeneration of donor-type immune cells. Higher numbers of total thymocytes and signal joint T-cell receptor excision circles were observed in the higher dose stem cell recipients, suggesting that accelerated regeneration of T cells was due to enhanced thymopoiesis. (Blood. 2004;103:4344-4352)

The role of B cells in the pathogenesis of graft-versus-host disease

Blood ◽  
2009 ◽  
Vol 114 (24) ◽  
pp. 4919-4927 ◽  
Author(s):  
Alexander Shimabukuro-Vornhagen ◽  
Michael J. Hallek ◽  
Rainer F. Storb ◽  
Michael S. von Bergwelt-Baildon
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Graft Versus Host Reaction ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Allogeneic hematopoietic stem cell transplantation is an established treatment modality for malignant and nonmalignant hematologic diseases. Acute and chronic graft-versus-host diseases (GVHDs) are a major cause of morbidity and mortality after allogeneic stem cell transplantation. T cells have been identified as key players in the graft-versus-host reaction and, therefore, most established drugs used against GVHD target T cells. Despite our knowledge on the pathogenesis of the GVH reaction, success of established therapies for prevention and treatment of GHVD is unsatisfactory. Recently, animal and human studies demonstrated that B cells are involved in the immunopathophysiology of acute and chronic GVHD. Early phase clinical trials of B-cell depletion with rituximab have shown beneficial effects on both acute and chronic GVHD. This review summarizes the current experimental and clinical evidence for the involvement of B cells in the pathogenesis of acute and chronic GVHD and discusses the clinical implications for the management of patients undergoing allogeneic stem cell transplantation.

scholarly journals Curing Ph+ ALL: assessing the relative contributions of chemotherapy, TKIs, and allogeneic stem cell transplant

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Adele K. Fielding
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplant ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Transplant ◽  
Older Individuals ◽  
Hematopoietic Stem

Abstract The understanding and treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia have changed rapidly in the past 10 years. The outcome is equally as good as for Ph− disease, and with targeted tyrosine kinase inhibitor therapies in addition to chemotherapy, the novel immunotherapy approaches, and the extension of allogeneic hematopoietic stem cell transplant (allo-HCT) to older individuals, there is the potential to exceed this outcome. There is particular interest in reducing chemotherapy exposure and considering for whom allo-HCT can be avoided. However, the patient population that can help test these options in clinical trials is limited in number, and the available evidence is often derived from single-arm studies. This paper summarizes outcomes achieved with recent approaches to de novo Ph+ acute lymphoblastic leukemia in the postimatinib era and helps integrate all the available information to assist the reader to make informed choices for patients in an increasingly complex field.

scholarly journals Clinical Outcomes of MDS Patients Who Were Allogeneic Hematopoietic Stem Cell Transplant Candidates but Did Not Proceed with Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2181-2181
Author(s):  
Rohan Gupta ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer K. Khaled ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Selection Bias ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
De Novo ◽  
Case Series ◽  
Cell Transplant ◽  
Consecutive Case ◽  
Hematopoietic Stem

Abstract Allogeneic hematopoietic stem cell transplant (alloHCT) remains the only potentially curative treatment for patients with myelodysplastic syndrome (MDS). However, this treatment is associated with significant risk of transplant-related mortality/morbidity such as graft-versus-host disease, infections, and regimen-related toxicities. Since there has been no "randomized" trial comparing between patients undergoing or not undergoing transplantation, the relative benefit of this treatment, particularly in elderly patients, is largely unknown. Retrospective comparative studies are significantly limited by the inherent selection bias of healthier/well-supported patients in the alloHCT group. Therefore, a critical knowledge gap exists regarding the survival outcome of MDS patients who are transplant eligible yet did not undergo alloHCT due to lack of suitable donors or other reasons. Herein, we retrospectively identified a consecutive case-series of 73 patients with MDS (excluding CMML), who were considered alloHCT candidates, based on initiation of an official donor search from 2005 to 2015, yet did not proceed with alloHCT. Median age at time of donor search was 60 years (range: 20-79) with the majority (63%) being male. Classifications of MDS were single or multi-lineage dysplasia (n=20), excess blast (n=39), MDS unclassified (n=6) or other/unknown classification (n=8). The cohort included 51 de novo MDS and 14 therapy-related MDS (t-MDS). Per International Prognostic Scoring System (IPSS) 29 patients (39.7%) were Intermediate (Int)-1, 14 (19.2%) were Int-2, and 23 (31.5%) were high risk at the time of donor search (Table 1). Reasons for no alloHCT were lack of donor (n=29), persistent/progressive disease (n=9), patient choice (n=13), or infections/complications after initiating the donor search (n=18). Treatments of these patients included chemotherapy (n=14), hypomethylating agents (n=61) and supportive care (n=23). Of the 73 patients, 15 (20.5%) had disease progression to acute leukemia at 1 year. There were 38 deaths with the median OS of 26.2 months (95%CI: 17.3-48.3 months). The 2-year probability of OS was 51% (95%CI: 36.7-62.9%). We next compared outcomes of these MDS patients who had a donor search without subsequent HCT to a consecutive case-series of MDS patients who underwent alloHCT from matched related and unrelated donors (cord blood and haploidentical transplants were excluded) during the same time period (n=276) at our center (Aldoss et al. Haematologica 2017). Patient demographics and MDS disease characteristics were similar between the two groups (Table 1). Median number of days from HLA typing to HCT were 168. By Kaplan-Meier method, OS (from the time of donor search) was significantly better for the alloHCT group (74% at 2-years) compared with non-HCT group (51% at 2-years), log-rank P<0.001 (Figure 1a). This survival benefit was primarily driven by the subgroup of patients with int-2/high risk IPSS. While the difference in the OS did not reach statistical significance in low/int-1 patients between HCT and non-HCT groups (OS probability at 2-years: 80% vs 68%, respectively, p= 0.182), the 2-year OS was significantly better (p<0.001) in the alloHCT group (67%, n=133) compared with non-HCT group (34%, n=37), when analysis was done in int-2 or high-risk patients. (Figure 1b) In an attempt to further assess the inherent selection bias, we analyzed and compared patients with no available donor (n=29, biologic assignment) with patients who did not receive HCT for other reasons (n=44). No statistically significant difference (p=0.13) was seen in the 2 year-OS (58% vs. 45%). In conclusion, using a unique cohort of patients who were referred for a donor search, our study in real-world practice demonstrates that transplant eligible MDS patients (at the time of donor search) who do not undergo alloHCT have worse survival outcomes compared to those undergoing transplantation. A prospective biologic assignment study is currently underway by the BMT CTN (#1102) to more definitively determine the impact and relative benefits of alloHCT in patients (≥50 years old) with Int2/high-risk de novo MDS. Disclosures Khaled: Alexion: Consultancy, Speakers Bureau; Daiichi: Consultancy; Juno: Other: Travel Funding. Salhotra:Kadmon Corporation, LLC: Consultancy. Ali:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau.

Feasibility and Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in High-Risk AML: Real-Life Perspective from a Single Institution

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4395-4395
Author(s):  
Marina Diaz-Beya ◽  
Miguel Angel Torrente ◽  
Alfonso Ardilla ◽  
Carles Serra ◽  
Nuria Martinez ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Median Time ◽  
De Novo ◽  
Conditioning Regimen ◽  
Real Life ◽  
Poor Performance Status ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem

Abstract Introduction: Allogeneic stem cell transplant (alloHSCT) is the treatment of choice in patients with high-risk acute myeloid leukemia (AML). However, it is uncertain exactly how many of these patients actually undergo alloHSCT as planned initially. Moreover, the real efficacy of this therapeutic option remains controversial. Since few studies have addressed these questions, to shed light on these issues, we have analyzed the results of a policy of early donor search, the proportion of patients in which initially planned alloHSCT was performed, and the outcome of alloHSCT in our center. Patients and Methods: We included in the study 246 AML patients (median age, 51 years, 16-70; 51% males) considered fit for intensive chemotherapy, who were treated according to 3 consecutive protocols of the Spanish CETLAM cooperative group (CETLAM-99, CETLAM-2003, and CETLAM-2012). Patients were diagnosed between 2003 and 2013 in our center or referred to our center for alloHSCT; median follow-up of alive patients was 70.4 months (12.5-143.8). Indication of allloHSCT in CR1 was established according to the stratification risk of each protocol, based on AML origin (de novo vs. secondary), cytogenetics, number of courses to achieve CR, NPM1/FLT3-ITD/CEBPA mutational profile, and MRD status at end of consolidation. Statistical analyses were performed using R v3.1 and SPSS v20. The effect of alloHSCT was analyzed by Mantel-Byar test with SCT as a time-dependent covariable. Results: AlloSCT was planned in 167 (68%) patients deemed of high-risk and it was actually performed in 130 out of these high-risk AML patients (78%). Types of donor were: matched related donor (MRD), n=63; 7/8 or 8/8 matched unrelated donor (MUD), n=51 (HLA matching: 8/8 or 10/10= 32; 7/8 and 9/10, n=19); unrelated cord blood (UCB) n=14; and family haploidentical donor, n= 2. Status at SCT was first CR (CR1) in 63 patients (48%), ≥CR2 n=23 (18%), and non-CR AML in 44 patients (34%). The type of conditioning regimen was myeloablative in 66 (51%) of the patients. Ninety-eight patients out of 167 patients with an indication for alloHSCT, lacked a MRD (59%). An unrelated donor search was performed in 80 (82%) out of these 98 patients, and was successful in 54 (67.5%). An UCB unit was selected in 14 patients without a MUD in a timely fashion. The main reasons for not initiating an unrelated donor search were poor performance status (n=5), refractory disease (n=4), and age (n=4). Median time from start of search to finding of an adequate donor was 50 days, and median time from start of search to SCT was 131 days. The overall outcome of these 167 patients with an indication of alloHSCT was 2-year OS: 48±8% and 5-year LFS: 36%±8% with a markedly better outcome among patients in whom alloHSCT was finally performed (2-year OS: 57±8% vs. 11%±10%; Mantel Byar, p<0.0001). The beneficial effect of alloHSCT was maintained in the subset of patients in CR1 for whom alloHSCT was planned (2-year OS: 60±12%; vs. 33±16%; Mantel Byar p=0.001). Intere stingly, the outcome of patients with an indication of alloHSCT did not differ between patients with an HLA-identical sibling and patients in whom a donor search was started (2-year OS: 50±12%; vs. 52±11%; p=0.97), in an intention-to-treat analysis. Moreover, the outcome of alloHSCT did not vary among different donor sources (MRD, MUD, and alternative donors) (2-year OS from alloHSCT: 59%±14% vs. 61%±18% vs. 44%±30, p= 0.6). Conclusions: A policy of early search of MUD enabled alloHSCT to be performed in the majority of patients for whom it was planned. Performing of alloHSCT in patients improved outcome of this cohort of high-risk AML patients, compared to patients not achieving alloHSCT. An adequate MUD was identified in a two thirds of patients, and a similar outcome was found after alloHSCT for all donor sources (MRD, MUD, and alternative source) in this study. Disclosures Rosiñol: Celgene, Janssen: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document