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.

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

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 Autologous Stem Cell Transplantation (ASCT) for the Treatment of Patients with Waldenstrom’s Macroglobulinemia / Lymphoplasmacytic Lymphoma (WM/LPL). a Risk Factor Analysis By the European Society for Blood and Marrow Transplantation (EBMT) Lymphoma Working Party

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 678-678 ◽  
Author(s):  
Charalampia Kyriakou ◽  
Ariane Boumendil ◽  
Herve Finel ◽  
Jean-Paul Vernant ◽  
Jan J. Cornelissen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Working Party ◽  
Disease Status ◽  
Female Gender ◽  
High Dose ◽  
Stem Cell Source ◽  
The Impact

Abstract WM/LPL is a rare distinct indolent lymphoma and the optimal management of the disease remains a major challenge. Combination therapies with old and novel agents have markedly improved the response rates and the quality of response but still the CR rates remain low and so far there is no cure. The role and timing of ASCT in the management of patients with WM/LPL has not been well established. The aim of the present study was to investigate the outcome of ASCT in early vs late WM/LPL. Methods: Eligible for this retrospective study were all patients who had a first ASCT for WM/LPL between 1995 and 2011 and were registered with the EBMT database. Baseline patient, disease, and transplant data were collected from MED-A forms. Statistical analysis used log rank tests to assess the impact of baseline characteristics on survival endpoints. Overall survival (OS) and disease-free survival (DFS) was estimated from the time of ASCT using Kaplan-Meier product-limit estimates. Curves of cumulative of non-relapse mortality (NRM) and incidence of relapse (IR) were compared by Gray’s test in a competing risk framework. Results: Altogether 615 patients fulfilling the inclusion criteria were identified in the database. The median age at ASCT was 53 years (range 19-76), and 428 patients (70%) were male. The median time from diagnosis to ASCT was 19 months (interquartile range: 10-51 months). 537 patients (71%) underwent ASCT after 2002. Disease status at ASCT was first partial (PR1), very good partial (VGPR1) or complete remission (CR1) in 325 patients, whilst 176 patients were autografted in second, third or later response, and 47 patients (4%) had primary refractory or progressive disease at ASCT. High-dose therapy was TBI-based in 82 patients (14%), and stem cell source was from peripheral blood in 598 patients (97%). With a median follow-up of surviving patients of 53 months, the 5-year OS was 65%, DFS was 46%, IR was 47% and NRM was 7%. IR was significantly lower in patients receiving ASCT in first response (CR1, VGPR1, PR1) compared to transplantation in subsequent complete or partial responses or with refractory disease (39% vs 53%; p=0.001), translating into a significant DFS (50% vs 40%, p= 0.004) and OS benefit (71% vs 63%; p= 0.033) for the patients transplanted early. DFS was significantly better for patients receiving ASCT after year 2000 compared to the patients transplanted before (p=0.031) and although the year of ASCT had influence on the OS this did not reach statistical significance (p=0.068). Multivariate analysis considering age, sex, disease status at ASCT, and ASCT year confirmed ASCT beyond 1st remission (HR 1.37, 95%CI 1.04-1.79), along with female gender (HR 0.73, 95%CI 0.54-0.97) and ASCT between 2001-2005 (vs before 2001; HR 0.66, 95%CI 0.47-0.92) as significant predictors of DFS. Conclusions: These results suggest that ASCT is a feasible and effective treatment for WM/LPL. Factors predicting for a favourable DFS are female gender, transplantation in the rituximab era, and ASCT in first remission. However, with DFS and OS of 40% and 63% at 5 years, even the outcome of patients undergoing ASCT with advanced disease is still encouraging. As single-hit ASCT can induce long term response with relatively low toxicity and economic burden, it may serve as benchmark for the upcoming novel targeted therapeutics entering the WM / LPL treatment arena. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Two Different Types of Rabbit ATG on Immune Reconstitution and Overall Results after Allogeneic Hematopoetic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in Children

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Camille Feltesse ◽  
Karima Yakouben ◽  
Mony Fahd ◽  
Marie Ouachee ◽  
Lou le Mouel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Immune Reconstitution ◽  
Lymphoblastic Leukemia ◽  
Effector Memory ◽  
Joint Models ◽  
Advisory Committees ◽  
Cd8 Cells ◽  
Stem Cell Source ◽  
Significant Difference

Introduction Thymoglobulin® and Grafalon® are 2 polyclonal rabbit anti-thymocyte globulin (ATG) used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent graft rejection and graft-versus-host disease (GvHD). Differences in manufacturing lead to different types and concentrations of antibodies in each product. Few studies compare their effects on post-transplant immune reconstitution: indeed, the latter is essential to prevent post-transplant infections as well as relapse (in case of hematological malignancies). Methods We conducted a retrospective study on children or adolescents who received a first unrelated allo-HSCT for an Acute Lymphoblastic Leukemia (ALL) between 2007 and 2018, in the department of pediatric hematology of the Robert Debré Hospital in Paris, France. During this time period, 2 types of ATG were used: Thymoglobulin® at 7.5mg/kg or Grafalon® at 60mg/kg. We included patients with a B or T phenotype ALL aged 2 to 18 years at the time of HSCT indication. Stem cell source could be from unrelated matched or mismatched bone marrow, peripheral blood or cord blood. All patients received a myeloablative conditioning regimen consisting of 12 grays total body irradiation and etoposide (60mg/kg). We compared patients for engraftment, counts of total lymphocytes, B and T lymphocytes, T CD4+ and CD8+ lymphocytes and their sub-types (naïve, effector memory, central memory and effector memory RA+), regulatory T cells, NK cells, and compared lymphocyte proliferation assays at 1, 3, 6 and 12 months after transplant. We used joint models of longitudinal and survival data to further analyze evolution of total lymphocytes, B and T cells, T CD4+ and T CD8+ cells, and NK cells. Finally, we compared clinical outcomes between the 2 groups. Statistical analyses were performed according to EBMT guidelines (Iacobelli, 2013). Results 76 children were included: 23 received Thymoglobulin® and 53 received Grafalon®. Stem cell source was peripheral blood or bone marrow for 61 patients and cord blood for 15 patients. Initial characteristics of patients, disease status and HSCT were similar between the two groups except for the median total nucleated cells and CD34+ progenitor cells of the graft, that were significantly higher in the Grafalon® group. We found a delayed cumulative incidence of engraftment in patients who received Grafalon® compared to those who received Thymoglobulin®: 29 days [interquartile range 22-36] versus 22 days [19.5-29.5], p=0.004. We observed significantly higher counts of total and T CD4+ lymphocytes 1 month after transplant in patients who received Thymoglobulin® as compared to those who received Grafalon®: 238/mm3 [172-466] versus 137/mm3 [51-306] respectively (p=0.005), and 40/mm3 [31.5-70.5] versus 16/mm3 [2.5-41.5], respectively (p=0.011). No differences in immune cell population counts were found 3, 6 and 12 months after transplant (figure 1). However, joint models found no difference in the evolution of lymphocyte subsets analyzed depending on the ATG used, except a non-significant difference in slopes over time for CD8+ cells (p=0.13). In patients given Thymoglobulin® compared to those given Grafalon®, we found a higher proliferation in response to stimulation by CD3 3 month after HSCT (CD3 index 20.4 [12.4;41] versus 5.9 [3.3;6.4] respectively, p=0.0039), and a higher proliferation in response to stimulation by adenovirus (ADV) antigen 1 year after HSCT (ADV index 78.6 [58.8;163.1] versus 15.7 [2.8;59.3] respectively, p=0.027). We found no effect of ATG type on overall survival (OS), disease-free survival (DFS), treatment-related mortality and chronic GvHD. In a multivariate analysis, we observed no effect of the type of ATG on OS and DFS. Conclusions We found a higher count of total and T CD4+ lymphocytes 1 month after unrelated allo-HSCT for ALL in children who received Thymoglobulin® at 7.5mg/kg compared to those who received Grafalon® at 60mg/kg. From 3 months after HSCT, we found no difference in immune reconstitution. Joint models for longitudinal data and survival found no significant difference in evolution of the lymphocyte subsets analyzed. Clinical outcomes were similar between the two groups. However, we compared an intermediate dose of Thymoglobulin® to a high dose of Grafalon® that is not still the standard in clinical practice. A prospective study comparing Thymoglobulin® to a lower dose of Grafalon® would be needed. Disclosures Baruchel: Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Bellicum: Consultancy. Dalle:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bellicum: Consultancy, Honoraria; Medac: Consultancy, Honoraria; Orchard: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees.

Bortezomib-Based Induction Therapy Induces Better Responses and Outcomes of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: The Results of Korean Multiple Myeloma Working Party Retrospective Study, KMM84

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5184-5184 ◽  
Author(s):  
Seok Jin Kim ◽  
Kihyun Kim ◽  
Jae Hoon Lee ◽  
Min Kyoung Kim ◽  
Jae-Yong Kwak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Conditioning Regimen ◽  
Working Party ◽  
Complete Response ◽  
High Dose ◽  
Significant Difference

Abstract Introduction: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) generally offers improved outcomes compared with conventional chemotherapy in patients with multiple myeloma. The disease status before ASCT such as the achievement of complete response (CR) was also reported as an important prognostic factor in multiple myeloma. Thus, the type and efficacy of induction therapy could affect the treatment outcome of ASCT because these induction chemotherapy regimens are designed to reduce myeloma burden leading to CR before ASCT. A combination chemotherapy regimen, VAD consisting of vincristine, doxorubicin, and dexamethasone is the induction therapy regimen which has been used for a log time. However, many new induction regimens have been used including thalidomide plus dexamethasone, and bortezomib since their efficacy was proven for relapsed or refractory multiple myeloma. However, the efficacy of these new induction therapy regimens and their effects on outcomes of ASCT has rarely been compared to VAD induction therapy. Methods: We performed a retrospective multicenter analysis supported by the Korean Multiple Myeloma Working Party (KMMWP). We have compared the efficacy of induction therapy regimens including VAD chemotherapy, thalidomide-based induction therapy, bortezomib-containing induction therapy, cyclophosphamide-based therapy. We also assessed the effects of these induction therapies on the outcome of ASCT in terms of response, relapse after ASCT, and survival. Results: We analyzed 344 patients who received induction therapy followed by high-dose chemotherapy with single ASCT at 13 hospitals in Korea. Patients who received tandem ASCT or ASCT followed by allogeneic stem cell transplantation were excluded. Their median age at diagnosis was 55 year old (range 20–72). The most common immunophenotype was IgG kappa and lambda (103, and 63 respectively) while 72 patients had light chain disease (kappa 30, lambda 42). 241 patients (70.1%) received VAD chemotherapy as an induction therapy prior to ASCT, and 35 patients (10.2%) received thalidomide-based chemotherapy before ASCT including thalidomide with/without dexamethasone. 46 patients (13.4%) were exposed to bortezomib including bortezomib alone or combined with other agents such as bortezomib, doxorubicin, dexamethasone (PAD). 22 patients (6.4%) received cyclophosphamide-based induction therapy. Age, sex, stage (Durie-Salmon and International staging system), and immunophenotype were balanced among these four groups of patients. Complete response (CR) rate including nCR (near CR) of VAD chemotherapy was 20.3% (49/241). CR rate of bortezomib and thalidomide-based therapy was 43.5% (20/46), and 37.1% (13/35) respectively. Cyclophosphamide-based induction therapy induced 27.2% of CR (6/22). Thus, CR rate of bortezomib-based induction therapy was significantly higher than other regimens (P &lt; 0.05). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. The melphalan-based conditioning regimen was used in all patients, and the dosage of melphalan was from 100mg/m2 to 200mg/m2. There was no difference of conditioning regimen among the four groups. When we assessed the response after ASCT, the results were as follows: VAD group (48 patients with continued CR, 85 patients with induced CR, 55.2% of CR rate), Thalidomide group (20 patients with continued CR, 12 patients with induced CR, 60.0% of CR rate), Bortezomib group (20 patients with continued CR, 12 patients with induced CR, 69.6% of CR rate), and Cyclophosphamide group (5 patients with continued CR, 7 patients with induced CR, 54.5% of CR rate). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. Relapse rate after ASCT was lower in bortezomib group (34.8%) than VAD group (63.1%), cyclophosphamide group (63.6%), and thalidomide group (54.3%). However, there was no significant difference of overall survival among these four groups. Conclusions: Bortezomib-based induction therapy might be more effective for improving CR rate in patients who received single ASCT. A further prospective study should be warranted to confirm whether this augmented response rate with bortezomib-based induction therapy might be translated into survival benefits.

Intravenous Busulfan (IV Bu)-Based Conditioning Regimen Before Allogeneic Stem Cell Transplantation (allo-SCT) for Adults with Acute Lymphoid Leukemia (ALL): A Aurvey From the Acute Leukemia Working Party of EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3005-3005
Author(s):  
Mohamad Mohty ◽  
Myriam Labopin ◽  
Miguel A. Sanz ◽  
Rose-Marie Hamljadi ◽  
Vladimir Koza ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Working Party ◽  
Adult Patients ◽  
High Dose ◽  
Myeloablative Conditioning ◽  
Lymphoid Leukemia ◽  
Stem Cell Source ◽  
Historical Series ◽  
Related Donor

Abstract Abstract 3005 Allo-SCT is an effective postremission therapy when compared to chemotherapy for adult patients with ALL. However, some studies suggested that the benefits from allo-SCT antileukemia effects are offset from the high non-relapse mortality (NRM), especially when using high dose TBI-based myeloablative conditioning. At present, it is well established that IV BU is as potent in inducing apoptosis of primary ALL cells as it is in AML. Marrow ablative or nonmyeloablative doses of IV BU were shown to be well tolerated in older adults when used as part of the conditioning regimen. With this background, this survey performed between 2000 and 2010, aimed to assess the outcome of 467 adult patients with ALL who received IV Bu-based conditioning regimen (without TBI) prior to allo-SCT. In this series, the median age was 37 years (range, 18–71) and the median year of allo-SCT was 2008. A B-lineage ALL was diagnosed in 317 cases (68%). 274 patients (59%) received allo-SCT from an HLA-matched related donor, while 168 patients (36%) received an HLA-matched unrelated graft (at least 6/6 match), and 25 (5%) received an HLA-mismatched graft. G-CSF-mobilized PBSCs were used as stem cell source in 387 cases (83%), and bone marrow in the remaining 80 cases (17%). At time of allo-SCT, 301 patients (64%) were in first CR, 88 patients (19%) in second CR and 78 cases (17%) in more advanced phases. As per inclusion criteria, all patients from this series received a conditioning regimen combining IV Bu and other chemotherapeutic drugs. 359 patients (77%) received a standard myeloablative conditioning (MAC) regimen (252 cases consisting of IV Bu 3.2 mg/Kg/day for 4 days and Cy; 77 cases IV Bu and Fludarabine, and 30 cases of IV Bu and other drugs). The remaining patients (23%) received a so-called reduced-intensity conditioning (RIC) consisting of nonmyeloablative doses of IV Bu (total dose ≤ 9.6 mg/Kg) and Fludarabine in the majority of cases (89%). In this series, 96% of patients achieved neutrophil engraftment at a median time of 15 days after allo-SCT. The incidences of grade II and grade III-IV acute GVHD were 18% and 10%, respectively. When considering patients in first CR who received transplant from an HLA-identical sibling, the cumulative incidence of NRM was 14±3% at 2 years. NRM was 29±8% at 2 years in patients transplanted in second CR from an HLA-identical sibling. In the unrelated transplant group, NRM incidences were 31±6% at 2 years for patients transplanted in first CR and 41±8% for patients transplanted in second CR. The cumulative incidences of relapse were 38±4% at 2 years for patients transplanted in first CR and 41±7% for patients transplanted in second CR using a matched related donor. In the unrelated transplant group, relapse rates were 31±5% at 2 years for patients transplanted in first CR and 44±8% for patients transplanted in second CR. With a median follow-up of 12 months (range, 1–88) after allo-SCT, leukemia-free survival (LFS) was 48±5% at 2 years for patients transplanted in first CR using an HLA-identical sibling. LFS was 30±8% at 2 years for patients transplanted in second CR using an HLA-identical sibling. In the unrelated transplant group, LFS rates were 38±6% at 2 years for patients transplanted in first CR and 15±6% for patients transplanted in second CR. In summary, results from this survey suggest that the use of IV Bu-based conditioning regimen may represent a valid option for the conditioning of adult ALL patients prior to allo-SCT. The use of IV-Bu-based RIC allowed a significant number of ALL patients not eligible to MAC to proceed to allo-SCT. Outcomes (NRM, LFS and relapse incidence) achieved after such regimens (especially in patients in first CR) compare favourably to figures from historical series using TBI-based conditioning, warranting a prospective randomized trial. Disclosures: Mohty: Pierre Fabre: Consultancy, Honoraria, Speakers Bureau. Nagler:Pierre Fabre: Honoraria.

PROSPECTS FOR HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE FIRST LINE OF THERAPY FOR AGGRESSIVE NON-HODGKIN’S LYMPHOMAS

2017 ◽  
Vol 63 (2) ◽  
pp. 326-328
Author(s):  
Larisa Filatova ◽  
Yevgeniya Kharchenko ◽  
Sergey Alekseev ◽  
Ilya Zyuzgin ◽  
Anna Artemeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
Hematopoietic Stem ◽  
Hodgkin's Lymphomas

Currently there is no single approach to treatment for aggressive diffuse large-cell B-cell lymphoma (Double-HIT and Triple-HIT). Accumulated world data remain controversial and, given the unfavorable prognosis in this subgroup, high-dose chemotherapy with autologous stem cell transplantation in the first line of treatment is a therapeutic option.

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.

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