Is There a Role for Autologous Stem Cell Transplantation (Auto SCT) for Patients with Acute Myelogenous Leukaemia? A Retrospective Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1689-1689
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas ◽  
Cecile du Toit ◽  
Andrew McDonald
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Entire Group ◽  
Myeloablative Conditioning ◽  
Post Transplant ◽  
Significant Difference

Abstract Abstract 1689 Introduction: To better counsel our patients on the role of auto SCT for patients with AML we studied consecutive individuals in CR 1 who had tissue compatible siblings and underwent allogeneic (allo) SCT with subjects who had no HLA donor and actually underwent auto SCT. Methods: Patients were in CR 1 following induction combinations containing 7 days of cyatarabine and etoposide with 3 days daunorubicin followed by similar consolidation therapy. The choice for the type of graft was based on availability of HLA identical siblings. Allogeneic donors underwent PBPC mobilisation with filgrastim and for GvHD prophylaxis grafts were exposed ex vivo to alemtuzumab 1mg/1010 mononuclear cells. Patients were prescribed cyclosporin until day 90 post transplant. Individuals lacking a donor underwent PBPC mobilization with etoposide 2 gr/m2 and harvested PBPC were cryopreserved. Patients received similar myeloablative conditioning followed by infusion of the grafts. Patients were stratified by clinical and laboratory factors as well as cytogenetic risk. The end points were TRM, DFS and OS. Results: The median presentation age for both transplant groups was 35 (14-60) years. Of the 112 consecutive patients achieving remission 37 had HLA identical siblings, but 3 relapsed and donors became unavailable in 2. Thus, autologous or allogeneic grafts were actually transplanted to 43 and 32 patients respectively. There was no significant difference in the presentation clinical features, laboratory parameters, marrow morphology or proportion of low and intermediate cytogenetic risk for both transplant options. Treatment mortality as well as relapse rate was similar (14 and 15%; 39 and 27%, respectively). At a median of 1609 and 1819 post transplant days, 56% and 63% in each group survive. In univariate analysis performance status, cytogenetic risk, morphological features of dysplasia, blast count and LDH were significant factors for survival. While for the entire group there was no difference in survival between both modalities, all patients with unfavourable cytogenetics receiving an autologous graft died of disease recurrence (3 year survival 35% vs 0%; p= 0.05). Conclusions: We conclude that patients with AML who have low or intermediate cytogenetic risk undergoing myeloablative conditioning followed by autologous or allogeneic T-cell depleted stem cell transplantation appeared to have similar outcome. However, those with unfavourable karyotype are unlikely to be cured with autologous grafts and are candidates for experimental modalities. Disclosures: No relevant conflicts of interest to declare.

The Effect of Prophylactic Administration of Myeloid Growth Factors Following Autologous Stem Cell Transplantation for Patients with Hematological Malignancies: A Systematic Review.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2192-2192
Author(s):  
Graeme A.M. Fraser ◽  
Ahmed Al-Sagheir ◽  
Donald M. Arnold ◽  
C. Tom Kouroukis ◽  
Ronan Foley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Early Administration ◽  
Post Transplant ◽  
Significant Difference ◽  
Duration Of Hospitalization

Abstract BACKGROUND. Myeloid growth factors (G-CSF, GM-CSF) are often administered following autologous stem cell transplantation to reduce the duration of neutropenia and limit infection-related morbidity and mortality. OBJECTIVES. (1) To determine if prophylactic myeloid growth factors (GF) administered to adult patients undergoing autologous stem cell transplantation for a hematological malignancy improve clinical outcomes post-transplant, and (2) to determine the optimal dose and schedule for the administration of GF post-transplantation. METHODS. Computerized databases were searched for reports from 1966 to March 2004. Reference lists from published reports were hand searched and published abstracts were also considered. Randomized trials comparing different GF regimens were selected by two independent assessors based on explicit inclusion and exclusion criteria; disagreement was resolved by consensus. Two independent reviewers blinded to authors, institution, journal name, and results used a validated scale to assess study quality. When possible, study results were pooled using a random effects model to obtain a pooled relative risk. RESULTS. Of 985 citations identified, 27 studies evaluating 2268 patients were included. Studies were grouped and analyzed according to their control and experimental arms: (1) early administration of growth factor (< day +3 post-transplant) compared with placebo or no growth factor (N=18 studies), (2) early administration of growth factor compared with delayed growth factor (> day +3, N=8 studies), and (3) high doses of GF (> 5ug/kg/d) compared to standard/low doses of GF (<5ug/kg/d, N=5 studies). Compared to no GF support, early administration of GF resulted in a statistically significant reduction in the median days to neutrophil engraftment (>0.5x109/L) in 14 of 15 studies (range 2–13 days). The magnitude of this benefit was diminished when only studies of higher methodologic quality and optimal transplant conditions (peripheral blood stem cells) were considered (range 2–3 days). A significant decrease in duration of hospitalization was reported in 8 of 15 studies; however no consistent benefit was observed for median days of i.v. antibiotics (3 of 10 studies), median days of fever (1 of 10 studies), or in the rate of microbiologically documented infections (RR 0.94, 95% CI 0.69–1.29). Compared to delayed administration of GF, early administration of GF was not associated with a significant difference in median duration of neutropenia any of 5 studies. Only 1 study reported a significant difference in the median duration of hospitalization and median days of i.v. antibiotics and it was of lower methodological quality. No difference in the rate of microbiologically documented infections was detected (RR 1.29, 95% CI 0.83–2.03). Compared to standard doses of GF, no study evaluating high dose GF reported a statistically significant improvement in any reported outcome but treatment was more costly owing to an increase in total GF administered. CONCLUSION. The administration of GF post-autologous stem cell transplant reduces the time to neutrophil engraftment and may reduce length of hospital stay. The effectiveness of delayed administration of standard dose GF (5 ug/kg/d) appears similar to strategies that initiate GF support immediately post-transplant or utilize high doses.

Comorbidities Index Is Not Predictive of Treatment Related Mortality in Patients (pts) Older Than 60 Years Treated with Reduced Intensity Conditioning and Allogeneic Stem Cell Transplantation (RIC-ALLO).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1180-1180
Author(s):  
Luca Castagna ◽  
Sabine Furst ◽  
Jean El Cheikh ◽  
Catherine Faucher ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Viral Infections ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 1180 Poster Board I-202 Benjamin Esterni, Didier Blaise Background: Allogeneic stem cell transplantation (ALLO) is the only curative therapy for many hematological malignancies. For many of these diseases, the median age at diagnosis is around the sixth decade of life, precluding myeloablative ALLO (MAC-ALLO). RIC-ALLO is less toxic and it has been performed in elderly pts, mainly affected by acute leukemia. Finally, comorbidities index seem to predict treatment related mortality (TRM) and overall survival (OS). Patients and methods: From 2001 and 2008, 67 pts older than 60 years (median age 63 y, range 60-70) received RIC-ALLO. Diseases were: acute myeloid leukemia 45%, multiple myeloma 18%, chronic lymphocytic leukemia 12%, non-Hodgkin lymphoma 10%, myelodysplasia 6%, plasmacellular leukemia 3%, others 6%. Disease status at RIC-ALLO was: complete remission 54%, partial remission 16%, and active disease 30%. RIC consisted of fludarabine-based with thymoglobulin 64%, or low-dose TBI-based 36%. Donors were: HLAid sibling 73%, matched unrelated 21%, and cord blood 6%. Previous autologous transplant was performed in 59% of pts. The median number of CD34+ and CD3+ cells infused was 5 (range 1-9.4) and 296 (range 84-704), respectively. Karnofski score was 60-80% in 25% and 90-100% in 75%; HCT-CI was 0 in 33%, 1-2 in 33%, and more than 3 in 34%; PAM score was 8-16 in 9%, 17-33 in 65%, 24-30 in 22%, and more than 31 in 3%; EBMT score was 2 in 22%, 3 in 36%, 4 in 28%, more than 5 in 12%. Results: The median follow-up was 22 months. The 2-y OS and PFS were 66.8% (IC95 [55.5-80.4]) and 52.4% (IC95 [39.5-69.5]), respectively. Grade II-IV acute graft versus host disease (aGVHD) and chronic GVHD (cGVHD) incidence were 49% and 43%, respectively. Early infections were fever of unknown origin in 42% of pts, bacterial infection in 6 cases, pneumonia in 8, and viral infections in 14. The early infection-related mortality was null. Late infections were bacterial in 3 cases, pneumonia in 1, viral infections in 6, and candidemia in 1. Seven pts died from late infective complications. Overall, the cause of death was toxicities in 18 pts and disease progression in 6 pts. The 100-d and 1-y TRM were 6.35% (IC95 [0.278-12.4]) and 24.2% (IC95 [12.9-35.4]), respectively. In univariate analysis, HCT-CI, EBMT score, and PAM score did not influence TRM or OS. Furthermore, age (60-65 vs 66-70) was not related to TRM. Conclusions: The aim of this retrospective study was to verify if TRM was excessively high in elderly pts, affected from several haematological diseases and receiving ALLO from different donors and after different RIC. A secondary objective was to evaluate if several comorbidities index could predict TRM and OS. This heterogeneity should be regarded as a more realistic view of general population. TRM was acceptable and not different when compared to younger pts as reported in literature. Furthermore, neither comorbidities index nor age help segregate a group of pts with different TRM. Disclosures: No relevant conflicts of interest to declare.

Long-Term Clinical Outcome of Children with Acquired Aplastic Anemia in Brazil.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4216-4216
Author(s):  
Marlene Pereira Garanito ◽  
Vicente Odone Filho ◽  
Marcela Vieira dos Santos ◽  
Elvira Velloso ◽  
Frederico L. Dulley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Cell Transplantation ◽  
Survival Probability ◽  
Conflicts Of Interest ◽  
Time History ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Abstract 4216 Introdution/ Backgound Acquired Aplastic Anemia (AAA) is a rare hematologic disorder characterized by pancytopenia and hypocelular bone marrow. The pathophysiology is immune mediated in most cases. Environmental exposures to drugs, viruses and toxins, are thought to trigger the aberrant immune response in some patients. However, 50 to 74 percent of cases are classified as idiopathic. The highest frequency occurs in young population (15 to 25 years) with a second peak at age of 65 to 69 years. Immunosuppressive therapy is the best treatment in children with AAA who do not have a suitable donor for allogeneic stem cell transplantation. Materials and methods We reviewed the medical records of patients diagnosed with severe (SAA) and very severe acquired aplastic anemia (vSAA) at the Department of Pediatrics, Instituto da Criança – Hospital das Clínicas, University of Sào Paulo, Brazil from December, 1992 to December, 2007. We analyzed the clinical characteristics of the patients at diagnosis and the response to immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). Results In this study, 47 patients (27 boys and 20 girls), younger than 16 years, were diagnosed with vSAA (n= 21) or SAA (n=26). The median age was 7,71 years, ranging from 0.5 to 16 years and the average time history (beginning of signs and symptoms related to the disease and diagnosis) of the disease was 4,82 months, ranging from 0,25 to 48 months. Of the 47 patients, 45 had idiopathic AAA and 2 had hepatitis-associated. The median follow-up was 6,91 years for the patients treated with IST and 3,10 years for the patients who underwent to HSCT. One patient died before any treatment. For the eight patients who underwent to allogenic HLA-matched HSCT the 5-years-survival probability was 50%. For the 38 patients treated with IST, ten of them received cyclosporine and a short course of corticosteroids (CsA/CE) and 28 received antithymocyte globulin plus cyclosporine (ATG/CSA). The 5 years survival probability was 40% and 55%, respectively (p:0,0054). According to the severity of AAA, we did not show a significant difference in survival (p:0,32). Eight patients received second treatment after 1 year and 6 months (6 ATG from different species and CsA, 1 CsA and 1 thalidomide) and the probably of survival at 5 years was 60%. Among the 18 patients who responded to IST, four relapsed (22%). Two patients developed acute myeloid leukemia at 5 and 12 years after diagnosis. Conclusion Our results both for patients undergoing HSCT, as well as patients undergoing IST are lower in comparison to other hematological centers. Probably, this discrepancy is related to the prolonged time of disease when patients are admitted to our service. Unfortunately, the difficulty of access to specialized centers for diagnosis and early treatment in our country is a reality and this fact contributes to the delay to the beginning of treatment. Disclosures: No relevant conflicts of interest to declare.

Improved Outcome with Busulfan, Melphalan, and Thiotepa Conditioning (BuMelTt) in Autologous Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Hodgkin Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3110-3110
Author(s):  
Tarunpreet Bains ◽  
Andy I Chen ◽  
Andrew Lemieux ◽  
Brandon Hayes-Lattin ◽  
Jose F. Leis ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Univariate Analysis ◽  
Disease Status ◽  
Significant Difference ◽  
Conditioning Regimens ◽  
Refractory Hodgkin Lymphoma

Abstract Abstract 3110 High-dose therapy followed by autologous stem cell transplantation (ASCT) is standard therapy for patients with relapsed or refractory Hodgkin Lymphoma (HL), although the optimal conditioning regimen remains uncertain. The three drug alkylating agent regimen, BuMelTt, has been established as our institutional regimen. We performed a retrospective review of outcomes obtained with BuMelTt compared to those achieved with other standard conditioning regimens. 133 patients with relapsed/refractory HL who underwent ASCT between January 1990 and December 2009 were analyzed. 62 patients received BuMelTt and 71 patients received other standard preparative regimens (Standard) consisting of CBV (44), CyVp16TBI (20), BEAM (4), CyTBI (2), and Mel (1). The median follow-up (range) was 4.3 years (0.01–14.24) in BuMelTt and 3.9 years (0.07–20.21) in Standard. The two groups (BuMelTt vs Standard) were balanced for gender (65% male vs 65% male), median age (29 vs 33), median number of prior regimens (2 vs 2), and pre-transplant disease status. Disease status was categorized as PR2/CR2 (48% vs 42%), primary induction failure sensitive (16% vs 17%), and Other which included PIF-refractory, 1st relapse refractory, and greater than 1st relapse (35% vs 41%). The 5 year overall survival (OS) was superior for patient who received BuMelTt conditioning (74% vs 54%, p = 0.03). There was also a trend for improved 5 year event free survival (EFS) for BuMelTt at 56% vs 39% for Standard (p=0.07). Other risk factors for outcome after ASCT were also analyzed and included disease status, more than 2 chemotherapy regimens before ASCT, Karnofsky score < 90% at ASCT, time from diagnosis to ASCT < 12 months, prior extranodal involvement, and age > 40 years. By univariate analysis, >2 chemotherapy regimens before ASCT (HR 1.7, p=0.05) and disease status of Other (HR 2.8, p<0.01) were predictive for lower OS. There was a trend for influence on OS for BuMelTt (HR 0.6, p=0.07) and PIF-sensitive (HR 1.9, p=0.09). By multivariate analysis, disease status of PIF-sensitive or Other predicted worse outcomes for OS (HR 2.4 & 2.9, p 0.03 & <0.01, respectively), and there was still a trend for benefit with BuMelTt (HR 0.6, p=0.09), although >2 chemotherapy regimens lost significance (p=0.22). For EFS, disease status of PIF-sensitive or Other were prognostic in univariate analysis (HR 2.1 or 2.3, p=0.02 or <0.01, respectively), and there was a trend for improved EFS with BuMelTt (HR 0.66, p=0.08). In multivariate analysis, disease status of PIF-sensitive or Other remained prognostic (p=0.03 & 0.004, respectively), while BuMelTt was not significant (p=0.27). There was no significant difference in 100 day non-relapse related mortality for BuMelTt vs Standard conditioning (5% vs 3%, p=0.88). More patients developed NCI CTCAE grade 3/4 mucositis with BuMelTt than Standard (89% vs 61%, p<0.01), but fewer patients had bacteremia with BuMelTt than Standard (7% vs 23%, p=0.02). There was no difference in duration of hospitalization, episodes of febrile neutropenia, incidence of veno-occlusive disease, time to neutrophil engraftment, or time to platelet engraftment. Our results suggest that BuMelTt may improve OS and EFS compared to standard conditioning regimens with increased but manageable toxicity. A case matched control study is planned. Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation For Acute Leukemias In Suzhou (China): Similar Outcome In CR1 Patients Compared With European Group For Blood and Marrow Transplantation (EBMT) Results: A Pair-Matched Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5527-5527
Author(s):  
Jia Chen ◽  
Yin Lu ◽  
Myriam Labopin ◽  
De Pei Wu ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Acute Leukemias ◽  
Blood And Marrow Transplantation ◽  
Significant Difference ◽  
Univariate Analyses ◽  
International Multicenter

Abstract The first affiliated hospital of Soochow University initiated a program of stem cell transplantation for hematological malignancies in 2001 and has done until December 2011 a total of 70 autografts to consolidate acute leukemias (61 adults and 9 children). The EBMT presently handles a registry with information on more than 450 000 transplants including over 100 000 transplants for Acute Leukemias, of which 22800 were autografts. In order to evaluate the outcome of patients transplanted in Suzhou and to compare it with results from the EBMT, we collected the necessary information on all patients transplanted in Suzhou and we did a pair matched analysis with patients reported to the EBMT registry. The median age of the patient population autografted in Suzhou was 32 years (4-63). The median follow up was 34 months (1-136). 59 patients (47 AML, 12 ALL) were autografted in CR1 and 11 in CR2/3. The majority of patients received a non TBI conditioning (87%) and PB as a source of stem cells (87%). For those autografted in CR1, the interval from CR1 to transplant was 203 days (75-404). At 2 years, the OS, LFS, RI and NRM were 73±7%, 52± 7%, 44±8% and 5±3% for AML and 76±14%, 67± 16%, 33±17% and 0% for ALL. 48 adult patients autografted in CR1 from Suzhou were matched with 89 patients from the ALWP EBMT registry. Matching factors were age ± 3 years, Cytogenetics and the number of induction courses to reach CR1 (1 course versus more than 1). Patients from Suzhou were transplanted more recently ; the interval from diagnosis to transplant was longer (242 days vs 172 days, p<0.0001) and TBI was less frequently used (p= 0.004 ). By univariate analyses the results were: Suzhou versus EBMT: OS 76 ± 6 vs 69 ±5 % (p= 0.33), LFS 55 ± 7 vs 60 ± 5% (p= 0.44), RI 40 ± 7 vs 33 ± 5% (p= 0.27), NRM 4 ± 3 vs 7 ± 3% (p = 0.47). By multivariate analyses adjusting for interval from diagnosis to transplant, year of transplant and use of TBI, there was no significant difference for OS (HR: 0.65, 95% CI: 0.19-2.19; p=0.49), LFS (HR: 0.97, 95% CI : 0.44-2.15; p=0.95), RI ( HR: 1.02, 95% CI : 0.46-2.28; p=0.96) . We conclude that the results from Suzhou are not statistically different from those obtained using the EBMT database. These findings as well as the observation in another study of similar outcomes following allogeneic transplants in China and within EBMT are important to consider when planning international multicenter randomized studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The importance of CD34 positive cell quantification for Hematopoietic stem cell mobilization

JBMTCT ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. p94
Author(s):  
Patricia Elkiki dos Santos
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Mononuclear Cells ◽  
Leukocyte Count ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Objective: The success of autologus hematopoietic stem cell transplantation relies on CD34+ cells' availability in peripheral blood (PB),  which is affected by several factors as age, sex, type of the disease, treatments, and others. In that regard, this prospective study aimed to evaluate the influence of these factors, correlating them with the pre-apheresis CD34+ cell count. Method: Before autologous hematopoietic stem cell transplantation, CD34+ cells were quantified in the pre-apheresis PB and the final product. Then, after the determination of minimum CD34+ value, clinical and laboratory parameters were compared between patients with higher and lower CD34+ cells count. Results: Out of the 34 patients, 29 presented more than 20,000 leukocytes/μl. Patients who failed in the mobilization presented <20,000 leukocytes/μl. There was a significant difference between the groups with different pre-apheresis CD34+ cells status regarding age (p=0.025), leukocyte count (p<0.001) and mononuclear cells (p=0.001) in PB. In addition, the pre-apheresis CD34+ ≥14 cells/μl group was related to a better yield of these cells in the final product and with the requirement of a single collection to obtain the minimum yield, of 2x106 CD34+/kg. Conclusion: This study demonstrates age and leukocyte count relate to CD34+ count in PB, and that CD34+ cells yield in the collection, can be predicted by  CD34+ cells frequency in PB.

scholarly journals Evaluation of Infectious Complications after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide Following Reduced-Intensity and Myeloablative Conditioning: A Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC) Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5758-5758
Author(s):  
Amandine Fayard ◽  
Fabien Tinquaut ◽  
Didier Blaise ◽  
Patrice Chevallier ◽  
Mauricette Michallet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Infectious Complication ◽  
Ex Vivo ◽  
Infectious Complications ◽  
Bk Virus ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is a major treatment for many hematological disorders. However, this treatment comes with significant risks linked to toxicity and infectious complications which may lead to death. Recently haploidentical transplants without ex vivo T-depletion have been developed through the use of post-transplant cyclophosphamide, thus reducing the risk of lethal GVHD. Toxicity data are still limited and few studies have evaluated infectious complications following haploidentical transplants without ex vivo T-cell depletion. In this study, we evaluated the incidence of infectious complications in patients who received haploidentical HSCT with post-transplant cyclophosphamide. Patients and methods: Data from 21 French centers and one Belgian center were retrospectively collected. Between January 2013 and December 2014, 159 patients all older than 18 years, affected with hematological malignancy and having undergone a haploidentical HSCT were included. Informed consent was obtained in accordance with the Declaration of Helsinki. Clinical data were obtained through ProMISe (Project Manager Internet Server), the internet-based system shared by all Francophone transplantation centers. Results: In total, 159 patients were included (Table 1). The median age at transplantation was 51.2 years (20-72 years). All patients were treated with post-transplant cyclophosphamide combined with an anticalcineurin and mycophenolate mofetil as GVHD prophylaxis. The median follow-up of the cohort was 14 months. Meanwhile, 49 patients (13%) developed acute GVHD (grade 2-4). Forty-three patients (27%) developed chronic GVHD. Median overall survival wasn't reached and the median progression-free survival was 571 days. At the end of the study, 69 patients had died, 29 were in relapse and 36 presented treatment related toxicity. TRM was of 14% and 22% at day 100 and 365 respectively. At least one infectious complication occurred in 135 patients. These were mostly clinically or microbiologically documented. Median time from transplant to the first occurrence of infectious complication was 12 days. Twenty five percent of patients presented between 3 and 5 infectious complications. The average number of infectious complications per patient was 2.9 (0-12). Sixty-two percent of early infectious complications occurred throughout conditioning or within 20 days post- transplant. Fifty-two percent of those infections were bacterial, 33% viral (39% of which related to CMV and 28% to BK virus), and 4.5% were parasitic or fungal (50% of which related to aspergillosis). Overall 436 infectious episodes were reported: bloodstream infections (62%) (bacteremia, viremia, fungemia or parasitaemia), respiratory (10%), urinary tract (8%), digestive tract (6%), skin (3%), septic shock and multi organ failure (6%), others (5%). Among those complications, 46% were bacteria related, 36% were virus related (17% of which due to BK virus and 39% to CMV), 7% were parasitic or fungal related (in these cases, 61% aspergillosis related). In total, 26 cases (6%) of BK virus infections were observed. Conclusion: In conclusion, in these preliminary results, except for maybe in the case of BK infections, incidence of infectious disease after haploidentical HSCT seem not to differ to related or unrelated HSCT. Further prospective studies are necessary to confirm these results, especially by evaluating infectious viremia with BK virus after HSCT haploidentical with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning for this patient population. Table 1: Patient disease and treatment characteristics Table 1 Table 1. Disclosures Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria.

Relevance and Factors Predicting for Early Lymphocyte Recovery After Allogeneic Bone Marrow Stem Cell Transplantation (BMT).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3053-3053
Author(s):  
Ulas D. Bayraktar ◽  
Rima M Saliba ◽  
Gabriela Rondon ◽  
Antonio Di Stasi ◽  
Partow Kebriaei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Proportional Hazards ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Allogeneic Bone ◽  
Limited Information ◽  
Grade Ii

Abstract Abstract 3053 Recovery of the immune system is critical for the success of allogeneic stem cell transplantation. Several groups, including ours, reported that faster lymphocyte recovery was associated with improved outcomes. There is limited information however, on factors affecting lymphocyte recovery and its influence on outcomes specifically after BMT. We retrospectively assessed 536 consecutive patients (pts) with acute leukemia (452 AML/MDS and 102 ALL) who underwent BMT (and engrafted) at our institution between 01/1999 and 12/2010 to determine 1) predictors of early lymphocyte recovery (ELR), and 2) influence on outcomes of ELR defined as achieving absolute lymphocyte count of 1000/μL (ALC1000) by day 100 after BMT. Characteristics of the study population including demographics, graft, disease, and transplant characteristics assessed are described in the Table. Conditioning regimens were classified as reduced intensity (RI), or high intensity (including TBI-, busulfan-, or melphalan-based) conditioning, as previously described. Cox's proportional hazards regression analysis was used to assess predictors of ELR and NRM on univariate and multivariate (MV) analysis. Pts who developed grade II-IV acute GVHD (aGVHD), received a second graft infusion, or relapsed before achieving ALC1000 were censored at the time of these events for the assessment of predictors of ELR. Only pts who were alive progression-free, and had not developed grade II-IV aGVHD by day 100 were eligible for the assessment of predictors of outcomes in landmark analysis starting on day 100 after BMT. Outcomes were assessed at the median follow-up in surviving pts of 40 months. On multivariate analysis, significant predictors of lower rate of ELR included TBI- or melphalan-based ablative conditioning (HR=0.5, p 0.003) (compared to RI or busulfan-based), and a haploidentical donor (HR=0.4, p 0.05). Preliminary analyses assessing CMV reactivation and grade II-IV aGVHD as time dependent variables showed these factors to be associated with higher and lower ELR, respectively. MV analyses incorporating these factors in prognostic model are ongoing and final results will be presented at the meeting. Among the 246 pts eligible for the outcomes assessment, ELR (HR=0.2, P <0.001) and remission status (CR1/CR2) at transplant (HR=0.3, P 0.004) were the only significant predictors of the rate of NRM on MV. The lower NRM rate in pts with ELR translated into higher overall survival on univariate analysis, yet this association was only significant at 1 year (HR1year 0.5, p=0.02; HR40 mo 0.7, p=0.2) after transplant. There was no impact for ELR on the rate of disease relapse at either one of these time points after BMT. In conclusion, early lymphocyte recovery is an independent prognostic factor for NRM after BMT. Lymphocyte recovery was influenced by the conditioning regimen, the use of a haploidentical donor and the development of aGVHD but not by the infused CD34 cell numbers or disease status at transplant. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation - A Long-Term Curative Approach In Patients ≥ 60 Years With Advanced Disease AML/MDS, - The Freiburg Experience Of 250 Consecutive Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2135-2135
Author(s):  
Hartmut Bertz ◽  
Michael Lübbert ◽  
Kristin Ohneberg ◽  
Ralph Wäsch ◽  
Robert Zeiser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Advanced Disease ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Stem

Abstract Since the introduction of reduced-toxicity conditioning prior to allogeneic hematopoietic stem cell transplantation (alloSCT) we transplanted from 1999 to 2012, 250 consecutive patients (pts) with myeloid malignancies (AML, MDS) aged ≥ 60 years (yrs). The 144 male and 106 female pts with a median age of 66 yrs (range 60-77) were transplanted for de novo AML (n=95), s/tAML (n=104) and MDS (n=51) with 89% unfavorable cytogenetics (CALGB). Since 2004 pts received a prospective fitness assessment (Deschler et al., Haematologica 2013). In 74% the donor was matched/mismatched unrelated and in 26% related. Only 16% were transplanted in CR1/2, 84 % with advanced or untreated disease. The conditioning regimen was the FBM protocol (fludarabine, carmustine, melphalan; Bertz et al., JCO 2003) in 98%, and 97% of the pts received PBSC. For GVHD prophylaxis in 91% a combination of cyclosporine plus alemtuzumab or ATG-F™ was used. At day +30, 94% of the pts had achieved CR by standard measures. With a median follow up of 57 months (3-157) 37% of the pts are alive; main causes of death were relapse (n=62), infection (n=35) and age-related diseases (n=13). The probability of OS/DFS was at 1yr 61%/49%, at 2 yrs 49%/41% and at 5 yrs 37%/34%, respectively. The probability for NRM at 1 yr is 24%. Nineteen known prognostic factors for outcome were evaluated: e.g. patient and donor age, graft size, days between diagnosis and alloHCT, CMV, early/advanced disease, cytogenetics, Sorror and Gratwohl score, donor type, HLA-identity. In the multivariate analysis a better OS (factors with p<0.1; table) was seen with a matched donor; a better DFS with a related donor, and high CD34+ graft content; in contrast, a mismatched donor is a risk factor for reduced DFS.TableMultivariate analysis of prognostic factors* for OS and DFSvariablevalueHazard Ratio95% CI lower limit95% CI upper limitP valueOverall survivalRemission at alloHCTadvanced1.370.862.160.1825HLA mismatchyes1.401.011.960.0463HCT-CI (Sorror)>= 21.311.011.960.1007Peripheral blood blastsyes1.210.841.760.3034Disease-free survivalRemission at alloHCTadvanced1.290.722.300.3946Donorrelated0.640.430.950.0258HLA mismatchyes1.440.992.090.0561CD34+ cells> median0.760.551.040.0867Bone marrow blasts> 5%1.210.781.880.3915*in univariate analysis p<0.157 (AIC criterion; Sauerbrei W, 1999 Applied Statistics,48:313-329.70.) In conclusion, this unique large cohort of older pts with AML/MDS with mainly advanced disease and unfavorable cytogenetics shows a high feasibility, safety and efficacy of alloHCT after the FBM protocol. AML/MDS pts in their 7th and 8th decade of life fit for transplant should be evaluated for alloHCT as very important long-term curative option. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cpit (Check Point Inhibitor Trial) 002: Phase I Study of Single-Agent and Combined Checkpoint Inhibition (CI) after Allogenic Hematopoietic Stem Cell Transplantation (alloHCT) in Patients at High Risk for Post-Transplant Recurrence

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5618-5618
Author(s):  
Jamie Koprivnikar ◽  
James K McCloskey ◽  
Rena Feinman ◽  
Robert Korngold ◽  
Michele L. Donato ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Dose Escalation ◽  
Acute Gvhd ◽  
Single Agent ◽  
Myeloablative Conditioning ◽  
Post Transplant ◽  
Tcr Repertoire

Background: AlloHCT is a potentially curative treatment for patients with acute myeloid leukemia (AML) and other myeloid malignancies (MM), however has a 40% relapse rate. The 2-year post-relapse survival rate is less than 20%; sustainable remissions are rare. Multiple strategies to mitigate relapse have been employed with variable degrees of success. An as yet untested approach involves manipulation of the T-cell milieu in the post-alloHCT setting using CI. Preclinical animal models of tumors have shown that blockade of PD-1 by monoclonal antibodies(mAbs) can enhance the anti-tumor immune response and result in tumor rejection, suggesting that host mechanisms limit the antitumor response. A murine model of an anti-PD-1 mAb given at the time of transplant showed that PD-1/PD-L1 interactions decrease acute GVHD, but increase chronic GVHD suggesting that PD-1 pathway modulation may provide unique opportunities for stimulating immune regulation post-alloHCT. Use of ipilimumab (I) to treat post-transplant MM resulted in a complete response rate of 42% and decreased the Treg/Tconv cell ratio, consistent with enhancement of the graft-versus-tumor effect. The CPIT-001 Trial demonstrated the feasibility and safety of combined CI with I and nivolumab (N) as consolidation following autologous stem cell transplantation (ASCT) for high-risk hematological malignancies as well as a 67% PFS rate at 18 months post-ASCT, a significant improvement as compared with historical data. Study Design: The study employs a 3x3 design with intrapatient dose escalation. Patients will alternately be assigned to receive either N or I as a single agent. If the safety endpoint is met for each group, enrollment to the combination CI group will open. See table 1 for dosing. For all Groups, intrapatient dose escalation will be utilized. If the patient tolerates 28 days of treatment, he/she will be escalated to the next dose level and the next patient will be enrolled. Enrollment must occur within 60 days prior to HCT conditioning to allow for collection of baseline samples. Patients will start CI therapy 60 to 100 days after stem cell infusion when acute GvHD is adequately controlled on a prednisone dose of 20 mg daily or less, organ function, and peripheral counts are adequate. Key inclusion criteria at study start up included patient age 75 years or less with high risk AML or MDS undergoing alloHCT with a matched-related or 10/10 unrelated donor who were receiving non-myeloablative conditioning. Bone marrow aspiration will be performed for response evaluation approximately every 3 months post CI initiation. The primary objective is to assess the safety of CI in this patient population. Secondary objectives include efficacy, assessment of blood immune reconstitution, phenotype and TCR repertoire by sequencing, assessment of tumor site immune phenotype, TCR repertoire and PD-L1/2 expression both prior to alloHCT conditioning and at relapse. The tertiary objective is to identify specific intestinal microbial strains associated with improved outcomes in alloHCT patients treated with CI. Microbial composition in stool samples of patients will be analyzed at screening, at engraftment, at various time points post-transplant, and at time of relapse, as it occurs. Study Experience Thus Far: The study opened to accrual in May of 2017. Four patients have signed informed consent. Two patients have been treated with CI. One patient withdrew consent prior to treatment and a second patient is currently status post alloHCT, but has not yet reached day 60. One patient received 2 doses of N and the second patient received 1 dose of I. Accrual to trial has been slower than anticipated. A detailed analysis of the patient screening log was completed. It was determined that 139 patients had been screened for trial. Major reasons for being ineligible included a diagnosis of ALL (34 patients; 24%), use of a haploidentical donor (30 patients; 22%), use of a full dose conditioning regimen (14 patients; 10%), diagnosis of CML (12 pateints; 10%), age greater than 75 (12 patients; 9%), diagnosis of CMML (12 patients; 9%). Following this analysis, an amendment was filed to include patients receiving haplo identical transplant and/or myeloablative conditioning, and to expand diagnosis to include all MM including CMML, CML blast crisis, and myelofibrosis. Disclosures Koprivnikar: Amgen: Speakers Bureau; Pfizer: Honoraria; Abbvie: Speakers Bureau; Novartis: Speakers Bureau. McCloskey:Jazz: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau; Novartis: Speakers Bureau. Rowley:Fate Therapeutics: Consultancy; Allergan: Equity Ownership. OffLabel Disclosure: Nivolumab - immunomodulation Ipilimumab - immunomodulation

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