scholarly journals Antithymocyte globulin administration in patients with profound lymphopenia receiving a PBSC purine analog/busulfan-based conditioning regimen allograft

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maxime Jullien ◽  
Thierry Guillaume ◽  
Pierre Peterlin ◽  
Alice Garnier ◽  
Amandine Le Bourgeois ◽  
...  
Keyword(s):  
Antithymocyte Globulin ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Absolute Lymphocyte Count ◽  
Standards Of Care ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Purine Analog ◽  
The Impact

Abstract Graft-versus host disease (GVHD) remains one of the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (ASCT). Prophylactic T cell depletion via antithymocyte globulin (ATG) during ASCT conditioning is one of the standards of care for GVHD prophylaxis, although the optimal dosing strategy is still unclear. Recent studies have reported that absolute lymphocyte count at the time of ATG administration could predict survivals in ASCT from unrelated donors. Here this issue was examined in 116 patients receiving peripheral blood stem cells (PBSC) ASCT with purine analog/busulfan-based conditioning regimens between 2009 and 2019 in our department. The impact of lymphopenia at the time of ATG administration was evaluated in terms of overall survival, disease-free survival and GVHD-free/relapse-free survival. After a median follow-up of 4 years, no adverse effect of a profound lymphopenia was observed on patients’ outcome. Notably, a reduced dose of ATG in patients with profound lymphopenia did not translate into better survivals. This study indicates that ATG can be administered whatever the recipient’s lymphocyte counts in patients receiving a PBSC purine analog/busulfan-based conditioning regimen ASCT.

Ruxolitinib Before Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Patients With myelofibrosis : a Preliminary Descriptive Report Of The JAK ALLO Study, a Phase II Trial Sponsored By Goelams-FIM In Collaboration With The Sfgmtc

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 306-306 ◽  
Author(s):  
Marie Robin ◽  
Sylvie Francois ◽  
Anne Huynh ◽  
Bruno Cassinat ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Renal Failure ◽  
Performance Status ◽  
Tumor Lysis Syndrome ◽  
Conditioning Regimen ◽  
Safety Data ◽  
Disease Free Survival ◽  
Inclusion Criteria ◽  
Hematopoietic Stem ◽  
Prophylactic Measures ◽  
The Impact

Abstract Ruxolitinib (RUXO) is a JAK inhibitor recently approved in France in patients (pts) with myelofibrosis (MF) because of its efficacy on splenomegaly and constitutional symptoms. Although no prospective safety data are available, many centers have started to use RUXO before HSCT to improve general performance status and decrease splenomegaly (influencing the engraftment). This academic study (ClinicalTrials.gov: NCT01795677) was designed to assess the impact of RUXO in pts with MF candidates for HSCT. Primary objective is the achievement of a disease-free survival at 1 year post HSCT > 50%. A total of 53 pts should be transplanted in order to reach this endpoint. Secondary objectives include: probability to be transplanted in pts with donor, overall survival, non-relapse mortality, hematological response, rate of pre-HSCT splenectomy, quality of life and MF-associated symptoms (through questionnaires). Inclusion criteria are: pts with MF, < 70 years, with either an intermediate or high risk MF according to Lille or IPSS score, or poor prognostic cytogenetics: complex karyotype, abnormalities of chromosomes 5, 7 or 17. Pts with platelets < 50 G/L, blasts ≥ 20% or previously treated with RUXO are excluded. After inclusion, RUXO is started at 15 mg BID in pts with platelets > 100 G/L or 10 mg BID in pts with platelets < 100 G/L and the search for a donor is started. If a donor is identified (related or unrelated HLA matched), the patient should be transplanted within 4 months. Pts without donors are prospectively followed on RUXO therapy in a parallel group. Conditioning regimen (CR) consists in melphalan and fludarabine, started after RUXO tapering and discontinuation. In May 2013, as some unexpected severe adverse events (SAE) were reported, investigators decided to stop enrollment of pts and to amend the protocol with new prophylactic measures. Twenty-three pts have been enrolled between Dec 2012 and May 2013 (1 pt excluded for inclusion criteria violation). Median age was 59 years (45-67). MF was primary in 19 and post essential thrombocytemia or polycythemia vera in 3 pts. All pts had splenomegaly (median: 23 cm). 12 pts had the JAK2V617F mutation. Cytogenetics were normal in 7, abnormal in 10 (poor prognostic in 2), missing or failed in 5 pts, respectively. Lille score was low in 5, intermediate (int) in 13 and high in 4 pts, resp. Age adjusted dynamic IPSS was low in 1, int-1 in 7, int-2 in 9, and high in 5 pts, respectively. Median follow-up was 149 days (69-229). Response after 2 months of RUXO was assessable in 16 pts: 50% partial remissions (- 25% in spleen size and improvement of constitutional symptoms) and 50% had stable disease. 8 pts have been transplanted (3 splenectomies before HSCT), 8 are waiting for HSCT, 4 pts have no donor identified yet and 2 pts were excluded from HSCT because of onset of comorbidities. Tolerance of RUXO was generally good and 3 SAEs were reported: febrile pancytopenia (n=2), multiple cranial nerve injury (n=1). The other SAEs (n=10) were reported within 21 days after RUXO discontinuation. Among the 10 pts who stopped RUXO, 7 had SAEs: multiple SAEs in 4, life-threatening in 7 and fatal in 2 pts, resp. Unexpected SAEs occurring after RUXO withdrawal included febrile cardiogenic shocks before HSCT not due to coronaropathy in 2 pts, and tumor lysis syndrome (TLS) with acute renal failure during CR in 1 pt. The 2 deaths were due to severe acute grade III-IV graft-versus-host disease refractory to steroids. The protocol was amended in May 2013 with TLS prophylaxis, modification of RUXO tapering with a shorter duration (10 days) systematically associated with steroids (0.5 mg/kg/day) and slight CR change (started with melphalan instead of ending). Despite this amendment, 2 other pts experienced TLS (but without renal failure) and 1 patient had a cardiogenic shock 9 days after HSCT. After review of the data with the Data Safety Monitoring Board, ethics committee and health authorities, the protocol is continued for the 22 pts already enrolled, but new inclusions are on hold until safety is confirmed. This preliminary report of the first prospective study assessing the impact of RUXO before HSCT in MF pts aims at highlighting unexpected SAEs, namely TLS (n=3) and cardiogenic shocks (n=3), that should be carefully considered in other prospective trials and clinical practice. According to the study design, all included pts should be transplanted before Oct 2013, and more information will be available for Dec 2013. Disclosures: Robin: NOVARTIS: gives ruxolitinib and a financial support for the JAK ALLO study Other. Kiladjian:Novartis, Celgene, AOP Orphan: Research Funding; Novartis, Sanofi, AOP Orphan: Honoraria; Novartis, Sanofi, AOP Orphan: Membership on an entity’s Board of Directors or advisory committees.

Updated Analysis of Hematopoietic Stem Cell Transplantations after Reduced Intensity Conditioning Regimen (RIC HSCT) for Hematological Malignancies from the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 45-45 ◽  
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Thomas Prebet ◽  
Mohamad Mohty ◽  
Jean Michel Boiron ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Grade Ii ◽  
The Impact ◽  
Global Population

Abstract This report updates a retrospective study from SFGM-TC registry concerning 738 patients who underwent RIC HSCT for hematological malignancies [280 F, 458 M, median age: 51 years (1–72)] between 1997 and 2004. The diagnosis were 173 AML, 40 ALL, 68 MDS, 152 NHL, 36 HD, 45 CLL, 70 CML, 154 MM; 332 patients have been previously transplanted. At time of conditioning, 261 patients were in CR, 224 in PR and 253 in progressive disease (PD). Peripheral blood stem cells (PBSC) were used in 574 patients and bone marrow in 164 patients from 655 HLA related donors and 83 unrelated donors. As conditioning, 152 patients received fludarabine and TBI (2 grays), 300 patients fludarabine, busulfan and anti-thymocyte globulins (FBS) (ATG 1d: 57, 2 d: 84, 3 d: 58, 4 d: 18, 5 d: 83) and 286 patients an other regimen. As GVHD prophylaxis, 722 patients received a cyclosporine A (CsA) based regimen. After transplant, 252 patients (35%) in the global population developed an acute GVHD ≥ grade II (grades III and IV: 116) and 208 patients (37%) in the PBSCT population (grades III and IV: 100). A chronic GVHD was present in 258 patients (38%) in the global population (115 limited and 143 extensive) and 221 patients (42%) in the PBSCT population (95 limited and 126 extensive). With a median follow-up of 27 months, the 3-year probability of overall survival (OS) and event-free survival (EFS) for the global population was 38% (33–44) and 28%(24–34) and for PBSC SCT patients 39%(33–46) and 32%(27–39) respectively. The 3-year probability of OS varied according to diagnosis (CLL: 62%, NHL:50%, CML:44%, MM:41%, MDS:37%, AML:26%, ALL:20%) and cGVHD (no:28%, yes:61%). The cumulative TRM incidence was 12% at 1 year and 13% at 3 years. A multivariate analysis was performed studying pre and post transplant factors for OS, EFS and GVHD:. Table 1 summarizes all variables showing a significant impact on OS and EFS. Furthermore, analyses showed the impact of one variable on AGVHD and cGVHD for PBSCT population: FBS with ATG 1day vs 2 days [HR:1.56(1.19–2.04) p=0.001, HR:1.50(1.14–1.97) p=0.003]. In conclusion, besides the influence of known factors on OS and EFS after RIC HSCT, this study pointed out, on a large series with a long-term follow-up, the major impact of disease status, acute and chronic GVHD and demonstrated the important role of ATG duration on GVHD incidence. Table 1: Multivariate analyses OS/EFS Variables OS (HR) p EFS (HR) p Conditionning :FBS ATG 1d vs 2 d Global 1.47 (1–2.2) 0,05 NS PBSC 1.6 (1.03–2.49) 0,04 NS FBS ATG 5d vs 2 d PBSC NS 1.13(1.04–1,24) < 0.01 PD vs CR Global 1.22 (1.1–1.32) < 0.01 1.15 (1.07–1.25) < 0.01 PBSC 1.2 (1.1–1,3) < 0.01 1.14 (1.05–1.24) < 0.01 Previous HSCT: yes vs no Global 1.27 (1.02–1,59) 0,04 1.25 (1.01–1.55) 0.04 AGVHD : Grade II vs 0-I PBSC 1.21 (1–1.47) 0,05 NS AGVHD : Grade III-IV vs 0-I Global 1,28 (1,14–1,43) < 0.01 1.12 (1–1.25) 0.04 PBSC 1.3 (1.14–1.47) < 0.01 1.13 (1–1.28) 0.05 cGVHD : yes vs no Global 0.2 (0.14–0.28) < 0.01 0.25 (0.19–0.35) < 0.01 PBSC 0.19 (0.13–0.28) < 0.01 0.25 (0.18–0.34) < 0.01

scholarly journals Impact of Cytogenetic and Molecular Markers on Disease-Free Survival of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3217-3217
Author(s):  
Yue Lu ◽  
Tong Wu ◽  
Xing-Yu Cao ◽  
Yan-Li Zhao ◽  
De-Yan Liu ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Leukocyte Count ◽  
Conditioning Regimen ◽  
Gene Mutations ◽  
Disease Free Survival ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Donor Source

Abstract Introduction: Cytogenetics is an independent prognostic factor in acute myeloid leukemia (AML). Molecular genetics including leukemia fusion gene, gene mutation and gene over expression are recognized to have significant impact on survival in patients with AML as well. In present study, the impact of cytogenetic and molecular markers on disease-free survival (DFS) of allogeneic hematopoietic stem cell transplantation (HSCT) for AML was investigated. Methods: Between April 2012 and December 2014, consecutive 345 patients with AML who underwent allogeneic HSCT in our center were analyzed retrospectively. All patients were either in poor-risk or in good-risk/intermediate-risk but with persistent minimal residual disease. The median age was 19 (1.8 to 64) years old. Children (≤14 years) were 96 (27.8%) cases and adults (>14 years) were 249 (72.2%) cases. Male to female was 200:145. The median disease course was 6 (1-64) months. Leukocyte count at diagnosis was < 30 x 109/L in 230 (66.7%) patients (low leukocyte) and ≥30 x 109/L in 115 (33.3%) cases (high leukocyte). Transplants at CR1, ≥CR2, and advanced disease were 168 (48.7%), 53 (15.4%) and 124 (35.9%), respectively. Donor sources were identical sibling (IS) in 45 (13.0%) cases, unrelated (UR) in 71 (20.6%) cases and haploidentical (HI) in 229 (66.4%) cases. Myeloablative conditioning regimens were administered with either Busulfan (Bu) plus Cyclophosphamide (Cy)/Fludarabine (Flu)-based in 285 (82.6%) patients or total body irradiation (TBI) plus Cy/Flu-based in 60 (17.4%) patients. Antithymocyte globulin was used in unrelated and haploidentical HSCT. Unmanipulated bone marrow and peripheral blood stem cells (PBSC) for IS and HI HSCT and PBSC for UR transplant were applied as the grafts. Cyclosporine, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Results: Univariate analysis showed that DFS after allogeneic HSCT in AML was not associated with patient age (children vs. adults, 70.3% vs. 69.4%, p=0.6), leukocyte count at diagnosis (low leukocyte vs. high leukocyte, 68.8% vs. 71.3%, p=0.8), donor source (IS vs. UD vs. HI, 77.3% vs. 76.8% vs. 65.8%, p=0.21), and conditioning regimen (Bu-based vs. TBI-based, 70.1% vs. 67.3%, p=0.45). Multivariate analysis indicated that disease status before HSCT was the only impact factor on DFS (CR1 vs. ≥CR2 vs. advanced disease, 81.6% vs. 70.0% vs. 53.1%, p<0.0001). Therefore, total 221 of 345 patients with AML in complete remission pre-conditioning were analyzed for impact of cytogenetic and molecular markers on survival after HSCT. DFS rates were 79.1%, 80.4%, 74.1% in good-risk, intermediate-risk, poor-risk cytogenetics groups (p=0.81), respectively. According to gene mutations, the DFS rates were 100% in CEBPA+, 91.6% in IDH1+/NPM1+, 85.7% in Flt3-ITD+, 81.5% in c-KIT+, 75.0% in no mutation, 70.2% in MLL-PTD+/ASXL1+/TET2+, 54.3% in Flt3-ITD+ with other mutations (p=0.42). According to gene expression, the DFS rates were 100% in DEK-CAN+, 100% in HOX11+/EVI1+, 84.8% in no abnormal gene expression, 83.3% in CBFb-MYH11+, 78.5% in WT1+, 76.5% in MLL+, 74.9% in AML1-ETO+, 0% in TLS-ERG+ (p=0.004). Conclusions: Under our HSCT protocol, disease status before transplant for the patients with AML has significant impact on DFS but not patient age, leukocyte count at diagnosis, donor source and conditioning regimen. Allogeneic HSCT has attenuated the influence of cytogenetics on DFS in patients with AML. Our preliminary data have shown that patients with CEBPA+, IDH1+/NPM1+, DEK-CAN+, HOX11+/NPM1+ have favorable survival, but patients with both Flt3-ITD+ and other gene mutations or with TLS-ERG+ have poor survival after allogeneic HSCT in AML. Disclosures No relevant conflicts of interest to declare.

scholarly journals Rabbit ATG Plus Cyclophosphamide with or without Fludarabine Is Superior Conditioning Regimen for Patients with Severe Aplastic Anemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2212-2212
Author(s):  
Parvez Ahmed ◽  
Tariq Mahmood Satti ◽  
Qamar Un Nisa Chaudhry ◽  
Kamran Mehmood ◽  
Nighat Shahbaz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Aplastic Anemia ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Severe Aplastic Anemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Group A ◽  
Group 2 ◽  
Group B

Abstract Objective: To compare rabbit antithymocyte globulin (ATG) containing conditioning regimen (group A) with horse antilymphocyte globulin (ALG)-based regimen (group B) for sibling allogeneic hematopoietic stem cell transplant (HSCT) outcome, disease free survival, rejection and complications in severe aplastic anemia patients. Methods: We analysed 205 aplastic anemia patients undergoing allogeneic HSCT from HLA matched sibling donors from July 2001 to April 2016. Group A (n=169) received conditioning with ATG plus Cyclophosphamide (CY) 200 mg/Kg with Fludarabine (Flu) 120mg/m2 (n=100) or without Flu (n=69), whereas group B comprised of CY plus ALG (n=36). The stem cell source was bone marrow (43.9%); PBSC (8.3%) and bone marrow plus PBSC (47.8%). Cyclosporin (CsA) was given as GVHD prophylaxis in 129 patients, while methotrexate (MTX) was added to CsA in 76 cases. Chi-square test was used to compare categorical variables. Kaplan Meier survival curves with log rank test was applied to compare the groups for survival analysis. Results: Overall survival was 78.7% in Group A compared to 69.4% in group B (p=0.23). Patients in group A had significantly better disease free survival (DFS) (75.1%) than group B (55.6%) (p=0.018). The incidence of acute GVHD was 18.3% in Group A compared to 22.2% in Group 2 (p=0.64), while chronic GVHD was significantly higher in Group 2 (22.2%) as compared to Group A (9.5%) (p= 0.04). Likewise frequency of Mucositis was high in Group B (30.5%) compared to Group A (10.7%) (p = 0.006). Moreover, patients receiving ALG-based conditioning had more frequent infections (86%) compared to ATG-based group (67.4%) (p=0.03). There was no significant difference within group A with respect to use of fludarabine as part of conditioning. Conclusion: Rabbit ATG containing conditioning regimen is associated with less complications and better survival in patients with severe aplastic anemia undergoing allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.

Allogeneic and Matched Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies Using a Modified Reduced Intensity Conditioning Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5324-5324
Author(s):  
Marion Raflores ◽  
James Rossetti ◽  
John Lister ◽  
Richard Shadduck ◽  
John Lech ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Reduced Intensity Conditioning Regimen ◽  
Disease Free ◽  
Related Mortality

Abstract INTRODUCTION:Use of a reduced intensity conditioning regimen (RICR) in hematopoietic stem cell transplant may result in lower treatment related mortality (TRM), less acute graft versus host disease (aGVHD) and better survivability, utilizing the graft versus tumor effect from HSCT. METHODS: Our institution’s original RICR protocol conditioning regimen (Trial A) consists of fludarabine 30 mg/m2 (Day-5 to D-2), melphalan 140–180 mg/m2 (Day -3) and ethyol 910 mg/m2 (Day-3) in addition to mycophenolate mofetil 1 g q12H and tacrolimus(serum level 5–15 ng/ml) beginning Day -3 as immunosuppressive therapy. Transplantation was done using peripheral blood stem cells from the best HLA-antigen match sibling (allo) or matched unrelated donor (MUD). We retrospectively compared transplant data from this original protocol to a modified RICR protocol (Trial B) using a lower dose of melphalan 100mg/m2 and addition of thymoglobulin 2mg/kg/d (D-2 to D0). RESULTS: 46 patients were transplanted in Trial A with median age of 46 years. 25 patients had allogeneic and 21 had MUD transplant. 30 patients were transplanted in Trial B with median age of 44 years. 22 patients had an allogeneic and 8 had a MUD transplant. All patients were heavily pretreated with 13 patients in Trial A and 9 patients in Trial B have undergone at least one previous stem cell transplant. At D30, all patients in Trial B were alive while 11% of patients in Trial A died of treatment related cause. At D100, 51% of patients in Trial A and 70% of patients in Trial B were alive. D100 TRM was 40% in Trial A and 20% in Trial B. Table 1. Treatment Outcome OS(%) TRM (%) RM (%) Trial A Trial B Trial A Trial B Trial A Trial B OS:overall survival TRM:treatment related mortality RM: relapse mortality 30 Days MUD 81 100 19 0 0 0 Allo 96 100 4 0 0 0 Total 89 100 11 0 0 0 100 days MUD 40 63 60 38 0 0 Allo 60 73 24 14 16 14 Total 51 70 40 20 9 10 1 year overall survival was 30% in trial A and 20% in Trial B. 1 year disease free survival (DFS) was 18% in trial A and 13% in Trial B. Table 2. 1 year treatment outcome* Overall Survival(%) Disease Free Survival (DFS) % Trial A Trial B Trial A Trial B *for Trial B, 5 living patients have not yet reached 1 year follow-up MUD 21 13 14 0 Allo 37 23 21 18 Total 30 20 18 13 Incidence of aGVHD≥2 in patients not receiving DLI and alive for more than 30 days post transplant was 56% in Trial A (MUD 67%, Allo50%) and 25% in Trial B (MUD63%, Allo 6%). At D100, aGVHD was the most common cause of death in Trial A while overwhelming sepsis was leading cause of death in Trial B. WBC engraftment with ANC&gt;500 was achieved in 98% of patients in Trial A and 93% of patients in Trial B. Average day of engraftment was 13 days in Trial A and 15 days in Trial B. Platelet engraftment with platelet count at least 20,000 was achieved in 80% of patients in both protocols with average day of engraftment at 18 days in Trial A and 21 days in Trial B. 95% of patients in Trial A had achieved at least 80% donor marrow cells at D100 while only 81% achieved this level of chimerism in Trial B. CONCLUSION: The modified RICR protocol for HSCT is a tolerable regimen which results in a lower incidence of D100 TRM and aGVHD but overall and disease free survival are not improved. Marrow engraftment is achieved although slightly delayed compared to the original protocol.

Incorporating Target Immunotherapy into Standard Conditioning Regimen Prior to Autologous Stem Cell Transplantaion (ASCT) Improves the Transplant Outcome for Pateints with Relapsed/Refractroy B Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1911-1911
Author(s):  
Mohamed I. Farhat ◽  
Reem Karmali ◽  
Stephanie A. Gregory ◽  
Parameswaran Venugopal ◽  
Mohamad Kassar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Background: Refractory or relapse B-NHL has a poor prognosis with conventional chemotherapy. Autologous stem cell transplant (ASCT) preceded by high dose chemotherapy has been the preferred therapeutic choice for such patients. The majority of the treatment failures occur within one to two years post transplant with disease progression after transplant accounted for most of the failures. The incorporation of targeted immunotherapy (rituximab) into the upfront and relapse setting is becoming of the standard of care for patients with B-NHL. The objective of this study is to evaluate the impact of rituximab (R) on disease free survival (DFS) when added to a standard conditioning regimen -- BEAM (carmustine, cytarabine, etoposide, and melphalan) prior to ASCT. Methods: A single institution retrospective analysis of 53 patients (pts), whom were heavily pre-treated, underwent ASCT between 08/98 & 07/06. All pts received rituximab in combination with high dose cytoxan for stem cell mobilization. 37 pts received R-BEAM and 16 received BEAM prior to ASCT. Actuarial rate for DFS was estimated from the day of SCT using the Kaplan-Meier method. Results: The group was predominantly men, 73% and 78%, with a median age of 57 years for both the R-BEAM and BEAM group. With a median follow up of 15.7 months, 13/37 (32%) and 11/16 (64%) pts who received R-BEAM and BEAM respectively developed disease progression after ASCT. The 2-yr actuarial disease-free survivals (figure1) were 60% and 21% for the R-BEAM and BEAM arm respectively (p=0.006). Conclusion: In this study, the outcome of pts who received R-BEAM compares favorably to those who receive BEAM alone with significant improvement in disease-free survival. Thus, incorporating target immunotherapy into standard conditioning regimen may have altered the natural history of the disease for pts undergoing ASCT for relapsed/refractory B-NHL. Disease Free survival Disease Free survival

Allogeneic Hematopoietic Stem Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) Not in First Remission

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4388-4388 ◽  
Author(s):  
Kendra L Sweet ◽  
Jeffrey E Lancet ◽  
Ryan Hillgruber ◽  
Megan Melody ◽  
Amina Llishi ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Secondary Aml ◽  
Mutational Status ◽  
The Impact

Abstract Background: Approximately 60 - 80% of AML patients achieve a complete remission [CR] with one or two cycles of induction chemotherapy, leaving many patients with refractory AML [PIF]. Unfortunately, the majority of patients in CR1 ultimately relapse. With salvage therapy, only 30-50% achieve CR2. Those with PIF or relapsed AML have shortened survival and few therapeutic options. Risk stratification is primarily based on karyotype, however other factors including age, initial white blood cell count, secondary AML and mutational status are also utilized to determine prognosis. HCT is an effective option for treatment of AML with intermediate/high risk features in CR1. It has also been utilized in refractory or relapsed disease. Advances in HCT over the last decade have improved overall survival (OS) and extended this option to older patients. Our aim is to characterize outcomes after HCT for AML patients who are not in CR1. Methods: We analyzed 136 AML patients who were not in CR1 at the time of HCT from 2004 - 2013. The conditioning regimen was fludarabine and myeloablative doses of PK targeted busulfan. IWG AML response criteria were used to define disease status at the time of transplant. Cytogenetic risk was based on the NCCN AML guidelines. OS is defined as the time from HCT until the time of death from any cause. Disease free survival (DFS) is defined as the time from HCT to the time of relapse or death from any cause. Results: Disease status consisted of 74 (54.4%) in CR2, 6 (4.4%) in CR3 or beyond, 27 (18.9%) were PIF, 21 (15.4%) with relapsed AML (REL) that was treated but still present at time of transplant, and 8 (5.7%) who received either no treatment or a hypomethylating agent (HMA). Median age was 52.0 (21.8 - 72.5) years, and 80 (59%) were male. Time from most recent treatment to HCT was < 1 month in 8 (5.8%), 1-3 months in 75 (55.8%), >3 months in 50 (36.8%) and not applicable in 3. Ninety-six (70.6%) had de novo AML, while 40 (29.4%) had secondary AML. Cytogenetic risk was favorable in 32 (23.5%), intermediate in 57 (42%), poor in 40 (29.4%) and unknown in 7 (5.1%). Graft-versus-host disease prophylaxis was tacrolimus with methotrexate or sirolimus, or mycophenolate mofetil. Donors included 41 (30.2%) matched related, 2 (1.4%) mismatched related, 65 (47.8%) matched unrelated and 28 (20.6%) mismatched unrelated donors. Peripheral blood stem cells were used in 97.2% of cases. Two year OS, DFS, cumulative incidence (CI) of relapse and CI-NRM for all patients was 45.3%, 35.2%, 47.1% and 18.2%, respectively. Two-year DFS stratified by disease status at time of HCT was 41.9%, 33.3%, 25.9%, 33.3% and 12.5% in CR2, CR3 or beyond, PIF, REL and HMA, respectively(p=0.011 for CR2 vs HMA) (Figure 1). Two-year DFS stratified by cytogenetic risk was 43.8%, 31.6%, 37.1% and 14.3% in favorable, intermediate, poor and unknown, respectively (p>0.05) (Figure2). CI-Rel stratified by disease status was 43.2%, 16.7%, 66.7%, 42.9% and 50% in CR2, CR3 or greater, PIF, REL and HMA, respectively (Figure 3). Conclusions: We analyzed 136 AML patients after undergoing HST outside of CR1 and the cumulative incidence of relapse at two years was 47%. Relapse was highest in those with primary induction failure or residual disease after either no or low intensity therapy. These data suggest that patients with active disease at the time of transplant fare worse than those who are transplanted in remission, highlighting the importance of effective upfront therapies in order to obtain the maximum potential benefit from HCT. Cytogenetic risk stratification did not significantly impact outcomes, although those with favorable risk cytogenetics trend towards higher 2-year DFS vs those with intermediate or poor-risk disease. Trials looking at the impact of maintenance therapy post-transplant may be valuable in this patient population. Table 1. Disease Status @ HSCT CR2 CR3 or beyond PIF RES HMA/untreated 2 years 41.9% (30.6 - 52.8) 33.3% (4.6 - 67.6) 25.9% (11.5 - 43.1) 33.3% (14.9 - 53.1) 12.5% (0.7 - 42.3) Table 2. Cytogenetic Risk Group Favorable Intermediate Unfavorable Unknown 2 years 43.8% (26.5 - 59.8) 31.6% (20.1 - 43.7) 37.1% (22.5 - 51.8) 14.3% (0.7 - 46.5) Table 3. Cumulative Incidence of Relapse CR2 (1) CR3 or beyond (2) PIF (3) REL (4) HMA/untreated (5) 2 years 43.2% (32.2 - 54.6) 16.7% (0.0 - 53.5) 66.7% (48.1 - 82.9) 42.9% (23.0 - 64.0) 50.0% (18.1 - 81.9) Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Sweet: Novartis Pharmaceuticals: Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Karyopharm Therapeutics Inc: Research Funding; Incyte: Research Funding. Lancet:Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy; Boehringer-Ingelheim: Consultancy; Pfizer: Research Funding; Kalo-Bios: Consultancy; Amgen: Consultancy. Perkins:PDL Biopharma: Research Funding. Field:PDL Biopharma: Research Funding.

Clinical Outcome of a Second Autologous Hematopoietic Stem Cell Transplant (HCT) for Non-Hodgkin (NHL) and Hodgkin Lymphoma (HL) Relapsing after a First Autotransplant.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3048-3048
Author(s):  
Sonali M. Smith ◽  
Koen van Besien ◽  
Jeanette Carreras ◽  
Julie M. Vose ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Disease Status ◽  
Large Cell ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Free Survival

Abstract Autologous HCT (autoHCT) salvages many patients (pts) with relapsed lymphomas but few relapsing after an autoHCT are cured. We determined feasibility of stem cell collection, engraftment kinetics, treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) for a second autoHCT (HCT2) for lymphoma relapsing after prior HCT (HCT1). We studied 35 pts, 20 with HL and 15 with diffuse or follicular large cell and immunoblastic NHL, receiving a HCT2 for relapse between 1986 and 2003 and reported to the CIBMTR. Median (range) age at HCT2 was 36 yrs (16–61); 61% had a performance score less than 90. HCT2 was performed >1 year after HCT1 in 80%. Median (range) time from diagnosis to HCT1 was 20 mo (4–162 mo), from HCT1 to relapse, 17 mo (3–68 mo), and from relapse to HCT2, 5 mo (1–40 mo). 83% underwent a 2nd stem cell / marrow harvest prior to HCT2. Median time to ANC >0.5 x 109/L was 11d. CBV or BEAM were the conditioning regimens for HCT1 in 80% and for HCT2 in 60%. The best response to HCT2 was complete remission in 22 pts and partial remission in 5; 8 pts had either no response or progressive disease. At a median follow up of 92 mo (32–124 mo) after HCT2, 26 pts (74%) have died with 17 (65%) dying of relapsed lymphoma. Two (6%) patients developed therapy-related MDS. The probability of TRM at day 100 was 12% (95% CI, 3–25%). The 1, 3 and 5 yr probability of PFS were 45% (95% CI, 29–62%), 33% (95% CI, 18–50%) and 30% (95% CI, 15–46%), respectively. The 1, 3 and 5 yr probability of OS were 63% (95% CI, 46–78%), 34% (95% CI, 19–50%) and 31% (95% CI, 17–47%), respectively. There were no differences in outcomes between HL or NHL. Pts relapsing >6mo after HCT1 appeared to have better OS (fig 1 and 2). In summary, HCT2 is feasible in pts with lymphoma after relapsing an HCT1. Stem cells harvested prior to HCT2 resulted in rapid engraftment with a day 100 TRM (12%) lower than that reported for alloHCT in this setting. Relapse is the primary reason for failure, but approximately one-third of pts enjoy long-term disease free survival. HCT2 should be considered for young pts with relapsed HL or NHL post-HCT1 without alternative transplant options. HCT1 (%) HCT2 (%) Sensitive disease status pre-HCT 26 (79) 24 (75) Stem cell source BM 15 (43) 10 (29) PBSC 13 (37) 21 (60) Both 7 (20) 4 (11) Median days to platelet recovery ≥ 20 x 109 /L 17 (7–376) 20 (1–101) Stem cell harvest between HCT1 and HCT2 29 (83) Different conditioning regimen for HCT2 25 (74) Outcomes TRM @ 1 yr 21 (9–37) PFS @ 5yrs 30 (15–46) OS @ 5 yrs 31 (17–47) Figure 1 Figure 1. Figure 2 Figure 2.

High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Salvage Treatment of Hodgkin’s Disease (HD): A Brazilian Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5103-5103
Author(s):  
Bruno K.L. Duarte ◽  
I.S. Valente ◽  
Afonso C. Vigorito ◽  
Francisco J.P. Aranha ◽  
Gislaine B. Oliveira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Gvhd ◽  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Bulky Disease ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract From May 1998 to November 2006, 77 HD patients who used the regimen of high dose cyclophosphamide HD (CY) 7 or 4g/m2, methotretaxe 8g/m2 and etoposide 2g/m2 followed by AHSCT were analyzed. Their median age was 25.8 (8.8–71.5) years, 46 males and 31 females. At diagnosis 50 (65%) were stage III or IV disease, 10 (13%) had bone marrow involvement, 29 (37.7%) bulky disease and 55 (71.4%) B symptoms. Besides that, all patients were submitted to a mean of 2 (1–4) chemotherapy lives and their status were 3 (3.9%) complete remission (CR), 17 (22.1%) partial remission (PR), 57 (74%) progression disease (PD) or in non-specified sensitivity relapse. Concerning CY dose 30 (39%) received 4 g/m2 and 47 (61%) received 7 g/m2. After the HDCY 16 (20.8%) were in CR, 22 (28.6%) PR, 28 (36.3%) remained in DP and 11 (14.3%) died most in PD. After a median follow-up of 3.97 (1.13–55.9) months, 53 (68.8%) patients were submitted to AHSCT and their present status is 30 alive [18 CR, 2PR and 10 DP]; 23 dead [2 CR, 14PD and 7 related to the procedure]. Overall survival for transplanted patients was 55% in 8 years. Currently we have 33/77 (43%) alive patients, 19 CR, 3 PR, 11 PD. Overall Survival (OS) for whole group was 32%, Disease Free Survival (DFS) 64% and Progression Free Survival (PFS) 40%. Patients who were in DP or relapse prior to the HDCY (57) compared to their status after that had a significant improvement (P=0,001), their OS was 40% to CR-PR group (24) versus 16% PD group (33). In general, mortality was 44 (57%), their cause was 19 PD (43.2%), 8 (18.2%) related to HDCY, 2 (4.5%) related to HDMTX, 7 (16%) related to AHSCT, 6 (13.6%) infections, 1 (2.3%) chronic GVHD after a reduced intensity conditioning regimen transplant and 1 (2.2%) AML. Besides that, 3 patients developed MDS and 1 developed AML. In conclusion, although it had happened a significant number of toxicity related deaths, the sequence is feasible, mainly for sensitive patients and presents an acceptable response. The authors emphasize the high frequency of poor prognosis patients and occurrence of MDS/AML in 4 (5.2%) patients.

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