Incidence of Invasive Aspergillosis in Allogeneic Stem Cell Transplantation Patients: An Italian Prospectic Multicenter Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5057-5057
Author(s):  
Nicola Mordini ◽  
Benedetto Bruno ◽  
Alessandro Busca ◽  
Roberto Sorasio ◽  
Mario Boccadoro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ct Scan ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Clinical Characteristics ◽  
Lymphoblastic Leukemia ◽  
Post Transplantation ◽  
Stem Cell Source ◽  
Optical Density Index ◽  
Cmv Reactivation

Abstract Between January 2003 and June 2004, every consecutive patient admitted for HSCT in three institutions was monitored for circulating galactomannan (GM) with Platelia Aspergillus assay (Bio-Rad) twice weekly from admittance until day 100, and then once weekly until day 365. Following fever occurence or GM optical density index increase (+ve cut-off value was >0.7), screening with weekly chest HR CT scan was started. Diagnosis of IA was made according to the EORTC/MSG criteria. 74 patients were analyzed, and 100 entered by now in the present study. Clinical characteristics of the patients are reported in table 1. We observed 10 cases of probable IA and 2 cases of possible IA. IA occurred before day 40 in 3 patients (median, day 13 after HSCT), between day 40 and day 180 in 8 cases (median, day 109 after HSCT), and after day 180 in 1 patient. Among the probable IA group of patients, 7/10 had GVHD, 6/10 were given steroids, and 3/10 had fever. Two consecutive positive GM test results were observed in the sera of 6/10 patients, GM was detected in BAL only in 3/10 cases and 1 patient had GM detected only in a SNC fluid. Chest CT scan was diagnostic in 8/10 cases, and in another patient CNS RMN scan shown lesions consistent with IA. All patients were lymphopenic at the time of IA diagnosis with an absolute count <450 mm^3, and only 1 patient was neutropenic. 3/10 patients had CMV reactivation during the IA episode and 4/10 had CMV reactivation in the 100 days following IA diagnosis. Cumulative incidence of IA after day 60 was 8,1%, overall incidence of IA was 16.2%, and probability of developing IA reached 24% at 1year after HSCT. Cumulative incidence of IA in the RIC group was 12.3%.6/12 patients died of IA, with a median survival of 24 days (range 1–83). IA accounted for 37.5% (6/16) of all deaths and for 55% of non-relapse deaths. 1-year survival in the IA group was 22% and 80% in non-IA group. Bimodal incidence distribution of IA after HSCT was confirmed, 25% of IA cases were diagnosed early (< day 40) after HSCT, 67% were diagnosed between day 40 and day 180, and an additional 8% developed after day 180. We confirm the role of GVHD and lymphopenia as important risk factors during the late post-transplantation periods. The relatively high incidence of IA could be a consequence of the increase of IA in recent years and of diagnostic improvement (GM+HR CT scan). We recommend the use of serial screening for GM after day 100 in patients lymphopenic or with GVHD. We need new diagnostic and therapeutic strategies for HSCT patients as IA accounts still for an unacceptable high portion of non-relapse deaths. Clinical characteristics of patients Patients 71 Disease Multiple myeloma 27 (38%) Myelodisplastic syndrome 8 (11.3%) Acute myeloid leukemia 9 (12.7%) Chronic myeloid leukemia 6 (8.5%) Hodgkin’s disease 5 (7%) Non Hodgkin’s lymphoma 8 (11.3%) Acute lymphoblastic leukemia 4 (5.6%) Chronic lymphatic leukemia 2 (2.8%) Aplastic anemia 1 (1.4%) Renal cell carcinoma 1 (1.4%) Mean age years (range) 48.8% (20–70) HSCT 74* HLA id RIC 52 (70.3%) MUD RIC 5 (6.8%) HLA id conventional 10 (13.5%) Syngeneic conventional 1 (1.3%) MUD conventional 5 (6.8%) MUD conventional UCB 1 (1.3%) Stem cell source PBSC 64 (86.5%) BM 9 (12.2%) UCB 1 (1.3%) Follow up days Median 214 Min 48 Max 595 GVHD Acute 53/74 (71%) Chronic 36/51 (70%) Chronic extensive 14/36 (39%) *Second transplant 3 patients

scholarly journals Low-Dose Decitabine Plus Venetoclax Maintenance Therapy Can Decrease the Relapse after Allogeneic Stem Cell Transplantation for MRD Positive High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-33
Author(s):  
Yunxiong Wei ◽  
Yaqing Cao ◽  
Xin Jin ◽  
Xiaoyuan He ◽  
Rui Sun ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Post Transplantation ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) and myelodysplasia (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable option for patients suffering from high-risk AML/MDS. However, there were still many patients relapsed after allo-HSCT, especially for some patients are MRD positive before transplantation. Novel therapy to prevent replase is urgently needed. Both BCL-2 inhibitor, venetoclax (VEN) and hypomethylating agent, decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration DEC has been shown to ameliorate GVHD and boost GVL post-transplantation. Several clinical trials have also shown that venetoclax plus decitabine can be a safety and effective salvage treatment for patients with AML/MDS relapsing after allo-HSCT. We therefore conducted a prospective study (ChiCTR1900025374) to exam the tolerability and efficacy of a maintenance therapy low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for MRD positive high-risk AML/MDS patients. To our knowledge, this is the first report of venetoclax combined decitabine in this setting. Methods: Six patients with MRD positive high-risk AML (n=5) /MDS(n=1) post transplantation were recruited. Around day 100 post transplantation, all patients received LDEC (15mg/m2 for 3 days) followed by VEN (200mg) on day 1 to 21. Two months is a cycle. The primary end points of this study were rates of Overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), incidence of cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD) and incidences of viral infection after allo-HSCT. Survival outcomes were analyzed using Kaplan-Meier analysis Results: Two of the six patients were partial remission (PR) before transplantation, and the remaining 4 patients were MRD+ before transplantation. The median follow-up was 16 (11-26.5) months. Both 2-year OS and 2-year EFS were 83%. The median 2-year EFS time was 16(9-26.5) months, and five patients still EFS alive at the time of this writing. The 2-year cumulative incidence of relapse after LDEC+VEN was 17% and 2-year non-relapse mortality was 0%. No tumor lysis syndrome (TLS) was observed. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 adverse events were observed in 33% (2/6). No grade&gt;3 AEs were observed. Acute (any grade) and chronic (limited or extensive) graft-versus-host disease occurred in 67% and 17% of patients, respectively. The 2-year cumulative incidence of CMV viremia and EBV viremia were 33.3% and 16.7%, respectively. Conclusion: We conclude LDEC+VEN can be administered safely after allo-HSCT, without evidence for increased incidence of GVHD, and this combination demonstrates decreased relapse for MRD positive high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent replase for MRD positive high-risk AML/MDS patients, and the clinical benefits need to be assessed in a comparative prospective trial. Figure Disclosures No relevant conflicts of interest to declare.

Reduced Intensity Versus Conventional Myeloablative Conditioning (RIC vs. MAC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Lymphoblastic Leukemia (ALL): A Survey from the Acute Leukemia Working Party of EBMT

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 793-793 ◽  
Author(s):  
Mohamad Mohty ◽  
Myriam Labopin ◽  
Tapani Ruutu ◽  
Alois Gratwohl ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Negative Impact ◽  
Therapeutic Option ◽  
Lymphoblastic Leukemia ◽  
Working Party ◽  
High Dose ◽  
Adult Age ◽  
Stem Cell Source ◽  
Significant Difference

Abstract The exact role of RIC allo-SCT for adult patients with ALL is still under considerable debate. While the use of such so-called nonmyeloablative or RIC regimens has emerged as an attractive modality to decrease transplant-related mortality, toxicity might represent only one aspect of the problem, since ALL encompasses a group of chemosensitive diseases, raising concerns that significant reduction of the intensity of the preparative regimen may have a negative impact on long-term leukemic control. In this multicenter retrospective study, the outcomes of 601 adult (age at transplantation >45 y.) patients with ALL who underwent transplantation in complete remission (CR) with an HLA–identical sibling donor, were analyzed according to 2 types of conditioning: RIC in 97 patients, and standard MAC (or high-dose) in 504 patients. Both groups were comparable in terms of gender, CR status (CR1 and CR2), interval from diagnosis to allo-SCT, and recipient/donor CMV serostatus. Patients in the RIC groups were older (median 56 y. vs. 50y in the MAC group; P<0.0001), Most of the patients in the MAC group received high dose TBI (80%), while the majority of the RIC regimens included either low-dose TBI or were ATG+chemotherapy-based regimens. The majority of patients (88%) from the RIC group received a PBSC graft. In the MAC group, the stem cell source consisted of bone marrow in 42% of patients. With a median follow-up of 13 months (range, 1–127), the incidences of grade II-IV and grade III-IV acute GVHD were: 35%, 14%, and 28%, 10% in the MAC and RIC groups respectively (P=NS). The cumulative incidence of non-relapse mortality at 2 years (NRM) was 32% (MAC) vs. 22% (RIC) (P=0.04). The cumulative incidence of relapse at 2 years was 30% (MAC) vs. 42% (RIC) (P=0.0007). However, the latter differences did not translate into any significant difference in term of leukemia-free survival (LFS) at 2 years: 38% (MAC) vs. 37% (RIC) (P=0.42). In multivariate analysis for LFS, the status at transplant was the only factor associated with an improved LFS (p<0.0001, RR=0.55, 95%CI, 0.42–0.72). The results of this retrospective registry based study suggest that RIC regimens may reduce NRM rate after allo-SCT for adult ALL when compared to standard MAC regimens, but with a higher risk of disease relapse and no impact on LFS. The latter represent promising findings, since patients who received RIC are likely to have serious comorbidities, which led the transplantation center to choose RIC, and surely most of these patients would not have received a standard allo-SCT in most institutions. Therefore, RIC allo-SCT for adult ALL (>45 y.) may represent a valid therapeutic option when a conventional standard conditioning is not possible, warranting further prospective investigations.

scholarly journals Bone Marrow Versus Mobilized Peripheral Blood Stem Cells for Non T Depleted Haploidentical Transplantations with Post Transplantation Cyclophosphamide in Acute Lymphoblastic Leukemia: On Behalf of the ALWP of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 589-589
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Emanuele Angelucci ◽  
Yener Koc ◽  
Mutlu Arat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Advisory Board ◽  
Post Transplantation ◽  
Peripheral Blood Stem Cells ◽  
Free Survival ◽  
Stem Cell Source ◽  
Cell Source ◽  
Blood Stem Cells

Background: The number of non T depleted haploidentical stem cell transplantations (haplo SCT) with post transplantation cyclophosphamide (PTCy) in adult patients (pts) with acute lymphoblastic leukemia (ALL) is increasing (Shemtov N et al, Leukemia 2019). Although the original haplo SCT with PTCy were performed with bone marrow (BM) grafts, the use of peripheral blood stem cells (PBSC) as the stem cell source may provide some advantages in engraftment and anti-leukemic effect which may be of special importance in ALL. Aim: The goal of this study was to compare BM to PBSC as stem cell source for non-T-cell-depleted haplo SCT with PTCy in adult pts with ALL in first or second complete remission (CR). Methods: The study was based on the haplo SCT with PTCy in adult pts with ALL that met the study inclusion criteria and that were reported to the European Society for Blood and Marrow Transplantation (EBMT) registry from 2010 to 2018. Multivariate analyses (MVA) were performed using the Cox proportional hazard model. Results: A total of 314 pts were reported, 157 of whom received BM and 157 received PBSC as the stem cell source. The median age at transplantation was 37 years (range, 18-68 years) and 36 years (range, 18-73 years), 66% and 62% were males, respectively. Diagnosis was Ph negative B-ALL in 39% and 41% of the pts, Ph positive in 32% and 34 % and T ALL in 29% and 25%, respectively.61% and 65% were in CR1, while 39% and 35% were in CR2. Pts and donor characteristics did not differ between the groups. More pts in the BM group received myeloablative conditioning (MAC), 87% vs 71% in the PBSC group, p&lt;0.0001. The cumulative incidence of engraftment at d60 was higher in the PBSC group compared to BM: 98% vs 93%, respectively p=0.0005. The incidence of 100 days acute(a) and 2y chronic(c) graft vs host disease (GVHD) were not significantly different between the BM and the PBSC graft source; Grade (Gr) II-IV 26% and 36%, III-IV 14% and 14%, total chronic 31% and 36% and extensive 12% in both, respectively. GVHD was the cause of death in 18% of pts receiving PBSC graft in comparison to 13% of those that received BM grafts. In MVA there was a trend for higher incidence of aGVHD II-IV HR 1.52 (0.973-2.38), p=0.065 and cGVHD HR 1.58 (0.995-2.51), p=0.053 in pts receiving PBSC vs BM grafts, respectively. Similarly, there was a trend for higher non relapse mortality (NRM) in the PB vs BM group HR 1.66 (0.99-2.8), p=0.056. There was no difference in relapse incidence (RI) HR 1.23 (0.76-2.0), p=0.416.While, leukemia free survival (LFS), overall survival (OS) and GVHD rel free survival (GRFS) were significantly better in pts receiving BM in comparison to PBSC graft HR 1.43 (1.0-2.03), p=0.047, HR 1.59 (1.08-2.34), p=0.018 and HR 1.42 (1.03-1.95), p=0.03, respectively. Conclusion: In pts with ALL in remission receiving haplo SCT with PTCy, the use of BM versus PBSC grafts resulted in better LFS, OS and GRFS. Disclosures Angelucci: Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorporated, and CRISPR Therapeutics: Other: Partecipation in DMC; BlueBirdBio: Other: Local advisory board; Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Partecipation in DMC. Socie:Alexion: Consultancy. Blaise:Molmed: Consultancy, Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

Prevention of Chronic GvHD after HLA-Identical Sibling Peripheral Hematopietic Stem Cell Transplantation with or without Anti-Lymphocyte Globulin (ATG). Results from a Prospective, Multicenter Randomized Phase III Trial (ATGfamilystudy)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 37-37 ◽  
Author(s):  
Francesca Bonifazi ◽  
Carlos Solano ◽  
Christine Wolschke ◽  
Francesca Patriarca ◽  
Massimo Pini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Infectious Complications ◽  
Peripheral Blood Stem Cells ◽  
Stem Cell Source

Abstract Introduction Allogeneic stem cell transplantation is a curative and increasingly used treatment approach for a variety of hematological malignancies. Late complications such a chronic graft-versus-host disease (cGvHD) is a major risk factor, which significantly influences morbidity and mortality after allogeneic stem cell transplantation (ASCT). The incidence of cGvHD is higher when peripheral blood stem cells are used as stem cell source. There is a strong need for preventing cGvHD after ASCT without increasing the risk of relapse. Patients and Methods We performed a multicenter, multinational, open-label, randomized study comparing anti-lymphocyte globulin (ATG-Neovii®) 10mg/kg on day -3,-2 and -1 with no ATG in 155 patients with acute myeloid (n=110) or lymphoblastic leukemia (n=45) in 1st complete remission (CR; n= 139) or 2nd CR (n=16) who received peripheral blood stem cells from their HLA-identical sibling (n=148) or relatives (n=7) after standard TBI (12Gy)/Cyclophosphamide (120mg/kg) or Busulfan (16mg/kg)/Cy (120mg/kg) based myeloablative conditioning regimen and sufficient organ function. Standard GvHD prophylaxis consisted of cyclosporine A and a short course of MTX (10mg/m² on day +1,+3,+6 and +11). Major inclusion criteria were: acute myeloid or lymphoblastic leukemia in 1st or 2ndCR, age 18-65 years, HLA-identical sibling or relatives, peripheral blood stem cell as stem cell source, and a myeloablative conditioning regimen. The primary study aim was to compare the cumulative incidence of cGvHD at 2 years after ASCT. Results Out of 161 randomized patients from 27 centers and 4 nations, 6 were withdrawn before conditioning and ASCT due to leukemia progression, or cancellation of the donor. 155 patients were analyzed for safety and efficacy; 83 were randomized to ATG and 72 to non-ATG. The treatment groups were comparable regarding recipient and donor age and sex, CMV serostatus, disease (AML vs ALL), 1st or 2ndCR. The median time to leukocyte (>1.0x10e9/l) and platelet (> 20x 10e9/l) engraftment was significantly delayed in the ATG group (18 vs 15 days, p< 0.001 and 20 vs 13 days, p<0.001). The incidence of acute GvHD grade I-IV was 25% for the ATG arm and 36% for the non-ATG arm (p=0.32) and for severe grade III/IV acute GvHD 2% and 7%, respectively (p=0.2). Regarding the primary endpoint, the cumulative incidence of cGvHD at 2 years was 36% % (95% CI 26-51%) in the ATG and 73% (95% CI 63-84% ) in the non-ATG arm (p<0.0001). In the ATG group 74% of the patients with any cGvHD had only limited episodes and 26% had an extensive episode, compared to 49% and 51% for non-ATG (p=0.04). There was no higher rate of infectious complications (58% for ATG vs 54% for non-ATG), CMV reactivation (22 vs 24%) and of EBV reactivation (2.4 vs 1.4%). The cumulative incidence of therapy related mortality at 2 years was 13% (95% CI 7-22%) for the ATG arm and 10% (95% CI 5-20%) for the non-ATG arm (p=0.57), resulting in 2 year relapse-free and overall survival of 59%% (95%CI 49-70%) and 75% (95% CI 66-85%) for the ATG group and of 65% (95% CI 52-77%) and 79% (95% CI 69-89%) for the non-ATG group (p=0.44 and p=0.20, respectively). Conclusion This randomized cGvHD prevention study provides evidence that ATG-Neovii® 3x 10mg/kg within a myeloablative preparative conditioning regimen for HLA-identical sibling peripheral blood stem cell transplantation is highly effective in preventing limited and extensive cGvHD without obvious increase of infectious complications and relapse, resulting in similar overall survival rates. Disclosures Kröger: Neovii: Research Funding.

scholarly journals Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies

2011 ◽  
Vol 68 (12) ◽  
pp. 1026-1032 ◽  
Author(s):  
Dragana Stamatovic ◽  
Bela Balint ◽  
Ljiljana Tukic ◽  
Marija Elez ◽  
Olivera Tarabar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Granulocytic Sarcoma ◽  
Allogeneic Transplantation ◽  
Stem Cell Source ◽  
Cell Source ◽  
Grade 3

Background/Aim. Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease - aGvHD) and delayed (chronic GvHD - cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). Methods. We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML) - 39, acute lymphoblastic leukemia (ALL) - 47, chronic myeloid leukemia (CML) - 32, myelodysplastic syndrome (MDS) - 10, Hodgkin?s lymphoma (HL) - 2, multiple myeloma (MM) - 3, granulocytic sarcoma (GrSa) - 3, severe aplastic anemia (sAA) - 22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one ?Large Volume Leukapheresis? (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 ?g/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (p < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT had a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the longterm OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.

scholarly journals Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantation

2021 ◽  
Vol 9 (2) ◽  
pp. e001818 ◽  
Author(s):  
Chantal Saberian ◽  
Noha Abdel-Wahab ◽  
Ala Abudayyeh ◽  
Hind Rafei ◽  
Jacinth Joseph ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Checkpoint Inhibitors ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Acute Myeloid

BackgroundImmune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.MethodsA retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.ResultsFour patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).ConclusionsICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

Outcome of Ethnic Minorities With Acute or Chronic Leukemia Treated With Hematopoietic Stem-Cell Transplantation in the United States

2005 ◽  
Vol 23 (28) ◽  
pp. 7032-7042 ◽  
Author(s):  
K. Scott Baker ◽  
Fausto R. Loberiza ◽  
Hongmei Yu ◽  
Mitchell S. Cairo ◽  
Brian J. Bolwell ◽  
...  
Keyword(s):  
United States ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Treatment Failure ◽  
Ethnic Minorities ◽  
Myeloid Leukemia ◽  
The United States ◽  
Post Transplantation ◽  
Hematopoietic Stem

Purpose We previously reported a higher risk of mortality among Hispanics after allogeneic hematopoietic stem-cell transplantation (HSCT). However, it is not known how specific post-transplantation events (acute or chronic graft-versus-host disease [GVHD], treatment-related mortality [TRM], and relapse) may explain mortality differences. The purpose of this study was to examine the relationship between ethnicity and post-transplantation events and determine their net effect on survival. Patients and Methods We identified 3,028 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myeloid leukemia reported to the International Bone Marrow Transplant Registry between 1990 and 2000 who received an HLA-identical sibling HSCT after a myeloablative conditioning regimen in the United States. There were 2,418 white patients (80%) and 610 ethnic minority patients (20%), of whom 251 were black (8%), 122 were Asian (4%), and 237 were Hispanic (8%). Cox proportional hazards regression was used to compare outcomes between whites and ethnic minorities while adjusting for other significant clinical factors. Results No statistically significant differences in the risk of acute or chronic GVHD, TRM, or relapse were found between whites and any ethnic minority group. However, Hispanics had higher risks of treatment failure (death or relapse; relative risk [RR] = 1.30; 95% CI, 1.08 to 1.54; P = .004) and overall mortality (RR = 1.23; 95% CI, 1.03 to 1.47; P = .02). Conclusion The higher risks of treatment failure and mortality among Hispanics may be the net result of modest but not statistically significant increases in both relapse and TRM and cannot be accounted for by any single transplantation-related complication. Further studies should examine the role of social, economic, and cultural factors.

scholarly journals Family Mismatched Donor Transplantation for Myelofibrosis: A Retrospective Analysis of the EBMT Chronic Leukaemia Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4655-4655 ◽  
Author(s):  
Kavita Raj ◽  
Eduardo Olavarria ◽  
Diderik-Jan Eikema ◽  
Liesbeth C de Wreede ◽  
Linda Koster ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Mismatched Donor

Abstract Background: Allogeneic stem cell transplantation is a treatment option for patients with advanced myelofibrosis. Problems encountered include an increased risk of delayed or poor engraftment and in the mismatched unrelated donor setting a higher rate of GVHD and particularly poor outcomes. As for other indications for allogeneic stem cell transplants, patients for whom either a matched sibling or matched unrelated donor is not available are considered for either a double umbilical cord blood, a mismatched unrelated donor or haploidentical stem cell transplant. Data on the latter option are limited and we reviewed registry data on all family mismatched donor transplants performed between 2001 and 2015 and reported to the EBMT registry. Results: Records retrieved 69 patients with myelofibrosis transplanted between November 2001 and November 2015. 44 (64%) were male. 50 (74%) had primary myelofibrosis,18 (27%) had secondary myelofibrosis (6 from ET, 5 from PRV and 7 others) and unknown 1(2%). Of 25 patients for whom the JAK2 V617F mutation status was known, 15 (22%) harboured the mutation. Patient Karnofsky performance status was > 70% in 98%. Of the mismatched family donors, 47 (68%) were male and 22 (31%) female. Donors were HLA mismatched at 1 locus in 12 (17%) and 2 or more loci in 48 (69%). Donor-recipient serology combinations were CMV -/- in 8 (12%), +/- in 4 (6%), -/+ in 15 (22%) and +/+ in 34 (49%) missing 8 (12%). Bone marrow was the stem cell source in 34 (49%) and peripheral blood in 35 (51%). The median total nucleated cell count (TNC) infused was 7.5x108/kg (range 2.3-21x108/kg) from data available in 17 patients. The median CD34+ cell dose was 6.9x106/kg (range 1.9-18.18x106/kg) from data available in 19 patients. Conditioning was myeloablative in 48 (70%) and RIC in 21 (30%) The conditioning regimes were varied but the predominant ones were Fludarabine, Busulphan, ATG (FBATG) and Thiotepa, Busulphan, Fludarabine (TBF). TBI was administered in 8 (12%) and in vivo T cell depletion in 22 (32%), ex-vivo T cell depletion in 5 (7%) patients. GVHD prophylaxis varied with post transplant Cyclophosphamide administered in 34/67 (49%) and ATG in 19/67 patients (28%). Neutrophil engraftment was established in 53 (82%) at a median of 20 days (range 11-83). Primary graft failure occurred in 8 (12%) and secondary graft failure in 4 (6%). This occurred at a median of 12 months (range 4.5-35 months). Eleven of these patients had a second allograft at a mean interval of 6.4 months. Responses to the first allograft (censoring for patients who had a second allograft) with data available in 45 patients, showed that complete remission was achieved in 35 patients (78%), 6 (13%) were never in CR and 4 (9%) were not evaluable. The cumulative incidence of grade II-IV acute GvHD at 100 days was 12% (95% CI 4-21%) and for grade III-IV acute GvHD at 100 days it was 5% (95% CI 3-11%). Data for chronic GVHD was valid in 49 patients. The cumulative incidence of chronic GvHD at 2 years was 62% (95% CI 47-76%). The cumulative incidence of limited cGvHD was 45% (95% CI 31-59%) whereas the cumulative incidence of extensive cGvHD was 10% (95% CI 2-19%). The median follow up was 24 months (95% CI 13-35 months). The 2-year OS was 51% (95% CI 37-76%) and the 5-year OS was 38% (95% CI 21-55%). The 2-year RFS was 44% (95% CI 30-59%) and the 5-year RFS was 31% (95% CI 15-48%). The 2 year cumulative incidence of relapse was 14% (95% CI 5-24%). The 2 year NRM was 41% (95% CI 28-55%), which increased to 54% (95% CI 37-72%) at 5 years. The main causes of death were infection (16, 24%), GVHD (7, 10%) organ damage or failure (3, 5%), relapse/disease progression (1, 2%) and secondary malignancy or PTLD (1, 2%). On univariate analysis there was no significant effect of recipient gender, donor gender, degree of HLA mismatch 1 vs >1 Ag MM, CMV matching between donor and recipient, primary or secondary MF, disease stage at transplant (chronic versus advanced phase), conditioning intensity, conditioning regimen, GVHD prophylaxis with ATG or post transplant cyclophosphamide or stem cell source on overall survival. Conclusion: Concerns regarding engraftment and secondary graft failure have excluded patients with myelofibrosis from clinical trials of mismatched related donor transplant. The data suggest that engraftment is feasible, and PFS and OS can be attained with limited severe chronic GVHD with family mismatched donors in this setting. Disclosures Ciceri: MolMed SpA: Consultancy.

scholarly journals Survival in Patients Who Underwent HLA-Haploidentical Stem Cell Transplantation in Two Centers in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Lisbeth Ramirez ◽  
Juan Manuel Herrera ◽  
Angela María Peña ◽  
Maria Luna-Gonzalez ◽  
Claudia Marcela Chalela ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Clinical Characteristics ◽  
High Dose ◽  
Post Transplantation ◽  
Hematopoietic Stem

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for several malignant and non-malignant hematological diseases. However, sometimes it is challenging to find human leukocyte antigen (HLA)-matched related or unrelated donors, especially in minority populations such as Hispanics. Transplantation of T cell replete HLA haploidentical graft (HaploHCT) followed by a high dose post-transplantation cyclophosphamide (PTCy) to eradicate alloreactive T cells is an option for populations with low donor availability. HaploHCT has emerged as an effective and safe strategy in this population (Luznik L et al. BBMT 2008), but data in Hispanics is scarce. Objective: The aim of our study was to describe the clinical characteristics and assess overall survival at 100 days, 1- and 3-years of patients who underwent haploHCT in two Colombian reference centers. Methods: An observational retrospective study was conducted at two tertiary referral centers in Colombia. Patients who underwent haploHCT at Clinica FOSCAL and Centro Medico Imbanaco between January 2013 and January 2020 were selected. Demographic and clinical characteristics where analyzed using descriptive statistics. The Kaplan-Meier method was used to assess overall survival (OS) rates and the log-rank test was used to compare survival rates between groups. All data were analyzed using R statistical software®. Results: Seventy-six patients were included. Mean age at transplantation was 34 years (range 18-60). Forty-two (57.89%) patients were female. Average body mass index was 19.86kg/m2. The majority of patients (57%) had a pre-transplantation ECOG performance status of 2. The most common indication for haploHCT was acute lymphoblastic leukemia (55.26%), followed by acute myeloid leukemia (23.64%). A sibling was the donor in 69.74% of the cases. Forty-seven (61.84%) patients were ABO-matched group. Peripheral blood stem cells were the graft source in 96% of the patients. The average number of infused CD34+ cells was 11.15 x 106/kg. Fludarabine-melphalan was the most commonly used conditioning regimen (57%), followed by fludarabine-busulfan-thiotepa (39%). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCy (50 mg/kg/day) on days 3 and 4 after HCT and a calcineurin inhibitor plus mycophenolate mofetil from day 5 to day 35 post-HCT. Median time to neutrophil engraftment (neutrophils &gt; 0,5x109/L) was 15 days (range 10-33), while platelet engraftment, defined as as the second day of unsupported platelet count of ≥20 × 109, occurred at a median time of 13 days (range 5-38) post-transplantation. On day 28 post-HSCT, 93.4% of the patients had achieved 100% chimerism. OS was 91% (95%CI 84-97.5) at 100 days, 81% (95%CI 72-90) at 1-year, and 77% (95%CI 68-88) at 3-years after HaploHCT. C onclusion: The results of our haploHCT retrospective study in a Hispanic population are comparable to several other cohorts that have reported similar outcomes of haploHCT compared to HLA-matched HCT. The OS rates reported in our study suggest that haploHCT is a viable option in patients without an HLA-matched related or unrelated donor available, especially in populations with lower rates of suitable donors. Acknowledgements: We deeply thank Gonzalo Gutiérrez García, M.D. for his leadership and guidance implementing the haploHCT program in Clinica FOSCAL. Disclosures Peña: Roche: Honoraria. Salazar:Janssen: Honoraria; Novartis: Honoraria. Sandoval-Sus:MorphoSys US: Consultancy; Janssen: Consultancy; Massive Bio: Consultancy; Celgene: Speakers Bureau. Sossa:Novo: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Roche: Honoraria.

scholarly journals HLA-DPB1 matching status has significant implications for recipients of unrelated donor stem cell transplants

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1220-1226 ◽  
Author(s):  
Bronwen E. Shaw ◽  
Steven G.E. Marsh ◽  
Neema P. Mayor ◽  
Nigel H. Russell ◽  
J. Alejandro Madrigal
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Matched Pairs ◽  
Hematopoietic Stem ◽  
Tissue Typing ◽  
Increased Risk ◽  
Cell Transplants ◽  
Risk Of Disease

AbstractStudies in unrelated donor (UD) hematopoietic stem cell transplantations (HSCT) show an effect of the matching status of HLA-DPB1 on complications. We analyzed 423 UD-HSCT pairs. Most protocols included T-cell depletion (TCD). All pairs had high-resolution tissue typing performed for 6 HLA loci. Two hundred eighty-two pairs were matched at 10 of 10 alleles (29% were DPB1 matched). In 141 HLA-mismatched pairs, 28% were matched for DPB1. In the 10 of 10 matched pairs (n = 282), the 3-year probability of relapse was 61%. This was significantly higher in DPB1-matched pairs (74%) as compared with DPB1-mismatched pairs (56%) (log rank, P = .001). This finding persisted in multivariate analysis. In the group overall (n = 423), relapse was also significantly increased if DPB1 was matched (log rank; P < .001). These results were similar in chronic myeloid leukemia (CML; P < .001) and acute lymphoblastic leukemia (ALL; P = .013). In ALL, DPB1-matched pairs had a significantly worse overall survival (log rank; P = .025). Thus, in recipients of TCD UD-HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status for the other HLA molecules. It is possible that this effect is especially apparent following TCD transplantations and invites speculation about the function of DPB1 within the immune system.

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