Myeloablative Chemo-Conditioning for First Hematopoietic STEM CELL Transplantation in Children with ACUTE Lymphoblastic Leukemia in First or Second Remission

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 546-546 ◽  
Author(s):  
Christina Peters ◽  
Jean-Hugues Dalle ◽  
Stelios Graphakos ◽  
Petr Sedlacek ◽  
Antonio Campos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Donor Type ◽  
Blood Stem Cells

Abstract Christina Peters, Petr Sedlacek, Jean Hugues Dalle, Stelios Graphakos, Antonio Campos, Akif Yesilipek, Jacek Wachowiak, Arjan Lankester, Andrea Pession, Amir Ali Hamidieh, Marianne Ifversen, Jochen Büchner, Gergely Krivan, Franca Fagioli, Arnaud Dalissier; Myriam Labopin; Peter Bader on behalf of the EBMT Pediatric Diseases Working Party Most children with acute lymphoblastic leukemia (ALL) with indication for allogeneic hematopoietic stem cell transplantation (HSCT) receive myeloablative conditioning with a total body irradiation (TBI)-containing regimen. To investigate the outcomes of patients (pts) who did not undergo TBI, we performed a retrospective registry based study on children below 18 years who received a myeloablative chemo-conditioning for a first allogeneic HSCT from different donors between 2000 and 2012. In this analysis, only chemotherapeutic regimens with more than 30 applications were included. In total, 732 pts were included: 313 pts who received bone marrow (BM) or peripheral blood stem cells (PBSC) in 1st CR, 247 pts with BM/PBSC transplantation in CR2, 85 pts and 52 pts who received umbilical cord blood (CB) in 1st or 2nd CR, respectively. The most commonly applied myeloablative chemo-combinations were: Busulfan (Bu)/Cyclophosphamide (Cy) (n=202), Bu/Cy/Etoposide (VP) (n=189), Bu/Cy/Melphalan (Mel) (n=93), Bu/AraC/Mel (n=80), Bu/Fludarabine (Flu)/Thiotepa (Thio) (n=62), Bu/Cy/Thio (n=53, Bu/Cy/Thio (n=53), and Bu/Flu (n=53). 313 pts received either BM or PBSC in CR1 with a median follow up of 26 months (1-156) and we compared Bu/Cy/VP vs the other chemo-conditioning regimens. The Bu/Cy/VP cohort had a longer follow up (med 37 vs. 20 months, p=0.002), pts were younger (med 3,6 vs. 6,5 years, p=0.003) and the median year of transplant was earlier (med 2009 vs. 2010, p=0.03). Donor type, CMV match, gender match, stem cell were comparable. In univariate analysis, conditioning with Bu/Cy/VP was better than all other combinations: relapse incidence (RI) 21% vs 32% (p=0.05), leukemia-free survival (LFS) 72 vs 54% (p=0.004), overall survival (OS) 79 vs 68% (p=0.03) and chronic GVHD (cGVHD) 9% vs 19% (p=0.014). Engraftment and incidence and severity of acute GVHD were similar and non- relapse mortality (NRM) was 7% vs 13% (p=0.10). Other significant influencing factors were: interval between diagnosis and transplantation below or beyond 208 days (NRM 6% vs 16%, p=0.015), donor sibling vs other (RI 35% vs 23%, p=0.01, NRM 5% vs 16%, p=0.001) and in vivo T cell depletion (TCD) vs no TCD (RI 35% vs. 19%, p=0.003; NRM 20% vs 4%, p=0.0001). In the cox model, conditioning type (Bu/CY/VP vs other), age, year of transplantation, interval from diagnosis to transplant, donor type, stem cell source and in vivo TCD were evaluated. For LFS only BU/CY/VP was associated with better outcome (p=0.004, HR .52), RI was lower after Bu/Cy/VP (HR .54, p=0.02), NRM was higher in pts older than 4,6 years (p=0.02, HR 2,48) and after TCD HSCT (p=0.01, HR 9,13) and OS was best after Bu/Cy/VP (p=0.03, HR 0.57). We conclude that omission of TBI is feasible for children who undergo first allogeneic HSCT in first or second complete remission. The combination of busulfan, cyclophosphamide and etoposide resulted in better LFS and OS with less NRM and RI for children who received bone marrow or peripheral blood stem cells in CR1. These observations should be the basis for prospective trials in homogenous patient groups. Disclosures No relevant conflicts of interest to declare.

Efficient and Durable Gene Marking of Hematopoietic Progenitor Cells in Nonhuman Primates After Nonablative Conditioning

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2271-2286 ◽  
Author(s):  
M. Rosenzweig ◽  
T.J. MacVittie ◽  
D. Harper ◽  
D. Hempel ◽  
R.L. Glickman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Nonhuman Primates ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells ◽  
High Level

Optimization of mobilization, harvest, and transduction of hematopoietic stem cells is critical to successful stem cell gene therapy. We evaluated the utility of a novel protocol involving Flt3-ligand (Flt3-L) and granulocyte colony-stimulating factor (G-CSF) mobilization of peripheral blood stem cells and retrovirus transduction using hematopoietic growth factors to introduce a reporter gene, murine CD24 (mCD24), into hematopoietic stem cells in nonhuman primates. Rhesus macaques were treated with Flt3-L (200 μg/kg) and G-CSF (20 μg/kg) for 7 days and autologous CD34+ peripheral blood stem cells harvested by leukapheresis. CD34+ cells were transduced with an MFGS-based retrovirus vector encoding mCD24 using 4 daily transductions with centrifugations in the presence of Flt3-L (100 ng/mL), human stem cell factor (50 ng/mL), and PIXY321 (50 ng/mL) in serum-free medium. An important and novel feature of this study is that enhanced in vivo engraftment of transduced stem cells was achieved by conditioning the animals with a low-morbidity regimen of sublethal irradiation (320 to 400 cGy) on the day of transplantation. Engraftment was monitored sequentially in the bone marrow and blood using both multiparameter flow cytometry and semi-quantitative DNA polymerase chain reaction (PCR). Our data show successful and persistent engraftment of transduced primitive progenitors capable of giving rise to marked cells of multiple hematopoietic lineages, including granulocytes, monocytes, and B and T lymphocytes. At 4 to 6 weeks posttransplantation, 47% ± 32% (n = 4) of granulocytes expressed mCD24 antigen at the cell surface. Peak in vivo levels of genetically modified peripheral blood lymphocytes approached 35% ± 22% (n = 4) as assessed both by flow cytometry and PCR 6 to 10 weeks posttransplantation. In addition, naı̈ve (CD45RA+and CD62L+) CD4+ and CD8+cells were the predominant phenotype of the marked CD3+ T cells detected at early time points. A high level of marking persisted at between 10% and 15% of peripheral blood leukocytes for 4 months and at lower levels past 6 months in some animals. A cytotoxic T-lymphocyte response against mCD24 was detected in only 1 animal. This degree of persistent long-lived, high-level gene marking of multiple hematopoietic lineages, including naı̈ve T cells, using a nonablative marrow conditioning regimen represents an important step toward the ultimate goal of high-level permanent transduced gene expression in stem cells.

Haplo-Identical Allogeneic Stem Cell Transplantation Using GCSF-Mobilized Marrow Plus Blood Stem Cells from Parent Donors for Children with High-Risk Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5084-5084
Author(s):  
Quanyi Lu ◽  
Xiaoqing Niu ◽  
Peng Zhang ◽  
Delong Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells

Abstract Increasing number of patients in China have difficulty of finding sibling donors due to limited number of siblings. We therefore explored the feasibility using haploidentical parent donors for allogeneic hematopoietic stem cell transplantation. Eight leukemia patients were studied in our hospital. These included 2 CML-BC, 2 MDS-RAEB, 3 relapsed ALL and 1 relapsed AML. The median age was 12 (7–17). GCSF- mobilized bone marrow and peripheral blood stem cells were collected from parents (1 to 3 locus mismatched). The conditioning regimen consisted of fludarabine (30mg/m2/d x5), bulsulfan (4mg/kg/d x3) and cyclophosphamide (50mg/kg/d x2). Cyclosporin A, mycophenolate mofetil, methotrexate, and ATG were used for GVHD prophylaxis. The total number of CD34+ cell in the grafts ranged between 5–10 x 106/kg. The median follow- up was 13 months (6–24). One patient failed to engraft, the other 7 patients achieved full donor chimerism at day 28. The incidence of acute GVHD (grade II-IV) was 57.1% (4 of 7). The incidence of chronic GVHD of limited stage occurred in the same 4 patients. One patient died of lung complication at 17th month, another patient with CML-BC relapsed 10 months after transplantation. The rest 6 patients are alive without disease. These results suggested that parents could be considered as stem cell donors in the absence of alternative donors for young patients with high-risk diseases. GCSF-primed bone marrow plus peripheral blood stem cells might be beneficial to reduce the risk of GVHD for leukemia children in China. More patients are needed to further study this approach.

Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation during First Complete Remission Following Imatinib-Combined Chemotherapy in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 462-462 ◽  
Author(s):  
Shuichi Mizuta ◽  
Masamitsu Yanada ◽  
Isamu Sugiura ◽  
Fumiharu Yagasaki ◽  
Toshiaki Yujiri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Philadelphia Chromosome ◽  
Combined Chemotherapy ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Donor Type

Abstract The treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has been changed dramatically since the introduction of imatinib. We previously reported a 96% complete remission (CR) rate in newly diagnosed patients treated with imatinib-combined chemotherapy (Yanada et al. J Clin Oncol2006;24:460–466), and showed that the combination therapy is useful in terms of providing patients with a better chance for receiving allogeneic hematopoietic stem cell transplantation (HSCT) in first CR. However, little is known about the outcome after allogeneic HSCT in such patients. To address this issue, we analyzed detailed data from 60 patients who underwent allogeneic HSCT in first CR following a uniform treatment protocol consisting of imatinib and chemotherapy. The median age of the studied patients was 37 years (range, 15–64 years), with 32 males and 28 females. Donors were HLA-matched related (n=24), matched unrelated (n=21), mismatched cord blood (n=9), and mismatched related (n=6). All 52 patients aged less than 55 years received a myeloablative conditioning regimen, whereas 6 of 8 patients aged 55 years or older received a reduced intensity conditioning (RIC) regimen. Grade 2–4 acute graft-versus-host disease (GVHD) was recorded in 20 patients, and chronic GVHD was recorded in 32 patients, 17 of whom had the extensive form. During a median follow-up of 2.6 years (maximum, 4.6 years) after transplantation, relapse and death in first CR occurred in 9 and 15 patients. The probabilities for overall survival (OS) and relapse-free survival (RFS) were 64% and 53%, respectively, at 3 years. Patients younger than 40 years had a trend toward better RFS than those at 40 to 54 years (60% vs. 38% at 3 years, p=0.16). Unexpectedly, all of the 8 patients aged 55 years or older remained alive in first CR. In relation to the donor type, RFS did not differ among patients allografted from a matched related donor, a matched unrelated donor, and mismatched cord blood (52% vs. 59% vs. 56% at 3 years, p=0.92). For risk factor analysis, the following variables were examined: donor type (sibling vs. unrelated vs. cord blood), age group (<40 years vs. 40–54 years vs. ≥55 years), minimal residual disease status at time of HSCT (quantitative real-time PCR negative vs. positive), type of conditioning regimen (RIC vs. myeloablative conditioning), performance status at time of HSCT, and bcr/abl isotype (major vs. minor). Multivariate analysis revealed that only the presence of major bcr/abl was significantly associated with inferior RFS (HR, 3.70; 95% CI, 1.34–10.2; p=0.012). Conclusion: In patients with Ph+ ALL who were initially treated with imatinibcombined chemotherapy, the outcome after allogeneic HSCT in first CR was favorable irrespective of the donor type. Cord blood transplantation and RIC transplantation might be attractive options for those without a suitable donor and for those unfit for conventional myeloablative conditioning, respectively. Prospective studies are warranted to confirm the roles of these forms of transplantation, especially RIC for patients between 40 and 54 years of age.

Encouraging Outcomes of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Lymphoblastic Leukemia in Second Complete Remission

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5933-5933
Author(s):  
Kohei Higuchi ◽  
Maho Sato ◽  
Osamu Kondo ◽  
Aya Ioi ◽  
Azusa Mayumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract [Background] We have been performing reduced-intensity stem cell transplantation (RIST) to avoid preconditioning-related complications. However, the effectiveness of RIST in pediatric patients with acute lymphoblastic leukemia (ALL) remains to be clarified. [Methods] We retrospectively reviewed 37 pediatric patients with ALL in second complete remission (CR2) who underwent first allogeneic hematopoietic stem cell transplantation (allo-SCT) between 1993 and 2012 in our institute. We compared the outcomes of RIST with those of myeloablative stem cell transplantation (MAST). [Results] The median age at allo-SCT was 9 years (range, 1 to 18 years). There were 33 B-lineage ALL, 3 T-lineage ALL, 1 lineage unknown ALL, and none of Philadelphia chromosome-positive ALL. Sixteen patients received HLA-matched bone marrow (7 related; 9 unrelated), 12 HLA-mismatched bone marrow (11 unrelated; 1 HLA haploidentical related), 4 cord blood, and 5 CD34 positive peripheral blood stem cells (HLA haploidentical related). In all patients, the 5-year overall survival (5y-OS) rate and the 5-year event free survival (5y-EFS) rate were 75.1% and 56.5%, respectively. Seven patients underwent RIST and 30 patients underwent MAST. The median follow-up durations of RIST and MAST groups were 3.3 years (range, 0.9 to 8.2 years) and 11.3 years (range, 0 to 21.2 years), respectively. The 5y-OS rates in RIST and MAST groups were 85.7% and 59.8%, and the 5y-EFS rates were 71.4% and 53.3%, respectively. The 5-year cumulative transplant-related mortality (TRM) rates in RIST and MAST groups were 0% and 31.0%, and the 5-year cumulative relapse rates were 28.6% and 24.3%, respectively. [Discussion] In our series, the cumulative relapse rate in RIST group was similar with that in MAST group, and the cumulative TRM rate in RIST group was lower than that of MAST group. Therefore, both of the 5y-OS and the 5y-EFS rates in RIST group seem to be better than those in MAST group. The outcomes of RIST in our series do not seem to be poorer. Although further studies are needed because of the small size of patients and short follow-up duration, RIST can be considered as the first transplantation for pediatric patients with ALL in CR2. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Reduced Intensity Versus Myelo-Ablative Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A Retrospective Study of the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3208-3208 ◽  
Author(s):  
Mathieu Leclerc ◽  
Régis Peffault de Latour ◽  
Mauricette Michallet ◽  
Didier Blaise ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Conditioning Regimen ◽  
French Society ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Donor Type ◽  
Conditioning Regimens ◽  
Disease Free

Abstract Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare form of acute leukemia associated with an overall bad prognosis. Only very few cases have been reported to reach durable remissions thanks to chemotherapy alone. Allogeneic hematopoietic stem cell transplantation (HSCT) using a myelo-ablative conditioning regimen (MAC) has been reported to be the gold standard treatment for BPDCN (Roos-Weil et al, 2013). However, little is known about the place of reduced-intensity/non-myelo-ablative conditioning regimens (RIC/NMA) in this setting. Methods We retrospectively collected from the database of the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) all cases of BPDCN treated with allogeneic HSCT. Immunophenotypes at diagnosis were centrally reviewed in order to confirm diagnosis according to the Garnache-Ottou diagnostic criteria (Garnache-Ottou et al, 2009). Twenty-eight patients had a diagnostic score of 2 or more. The remaining 15 patients all had CD4+ CD56+ disease, but as they were mostly diagnosed before publication of this score, other markers (such as CD123, BDCA-2 and BDCA-4) were not performed routinely at that time, precluding calculation of a score at least equal to 2. Results From February 2003 to January 2014, 43 patients with BPDCN received an allogeneic HSCT in 21 French centers. PatientsÕ characteristics are summarized in table 1. Median age was 57 (range: 20-72), sex ratio (M/F) was 2.1/1 and most patients were in CR1 at time of transplant. Sibling transplantation was performed in 42% of cases. Peripheral blood was the main source of stem cell used in this study (70% of cases). Conditioning regimens were MAC in 18 cases (42%) and RIC/NMA in 25 cases (58%, table 2). Four patients (9%) had engraftment failure or secondary graft rejection, 3 of whom having received cord blood units. All these 4 patients were transplanted again 2 to 17 weeks after the first transplant. After a mean follow-up of 668 days for the entire cohort (1050 days for alive patients), 22 patients (51.2%) were alive, 19 of whom being disease-free (44.2%). Eleven patients had relapsed, at a median of 225 days post-HSCT (range: 74-821 days). Two-year cumulative incidences of relapse (CIR) and non-relapse mortality (NRM) were 25.5% (95% CI = [0.13-0.40]) and 32.8% (95% CI = [0.186-0.479]) respectively (figure 1). At 2 years post-transplant, disease-free survival (DFS) and overall survival (OS) were 44.9% (95% CI = [0.291-0.595]) and 52.2% (95% CI = [0.357-0.664]), respectively. Even though not statistically significant, patients receiving a MAC (n = 18) were less likely to relapse than patients receiving RIC/NMA (2-year CIR = 7.1% and 36% respectively, P = 0.137), but had a higher NRM rate (43.9% versus 26% at 2 years, P = 0.419), resulting in similar 2-year DFS and OS (57.1% versus 38%, P = 0.511 and 57.1% versus 49.7%, P = 0.91). There was a trend for a lower incidence of NRM at 2 years in patients transplanted from a sibling donor versus others (16.7% and 39.9% respectively, P = 0.0505, figure 2), but donor source had no effect on CIR (P = 0.826), DFS (P = 0.194) and OS (P = 0.188). Conclusion In this series of 43 patients with BPDCN, allogeneic HSCT was associated with a good disease control, but NRM was high. In this regard, transplantation from a sibling donor appears to be the best option. RIC/NMA are feasible and may also reduce the incidence of NRM, but at the expense of a higher incidence of relapse. Table 1. Patients' characteristics N 43 Age 57 (20-72) Sex (M/F) 29/14 Time from diagnosis (days) 170 (107-1050) Disease status at HSCT  CR1 34 (79%)  CR2 5 (12%)  No CR 2 (5%)  Unknown 2 (5%) Donor  Sibling 18 (42%)  Unrelated 23 (53%)  Mismatch relative 2 (5%) Cell source  Bone Marrow 7 (16%)  Peripheral Blood 30 (70%)  Cord Blood 6 (14%) Conditioning regimen  MAC 18 (42%)  RIC/NMA 25 (58%) CMV status (D/R)  -/- 18 (42%)  -/+ 9 (21%)  +/- 4 (9%)  +/+ 12 (28%) GVHD prophylaxis  Ciclo/MTX 15 (35%)  Ciclo/MMF 19 (44%)  Ciclo alone 5 (12%)  Other 2 (5%)  Unknown 2 (5%) Table 2. Conditioning regimens MAC 14 Cy/TBI 11  Cy/TBI 12 Gy 9  Cy/TBI 10 Gy 1  Cy/Flu/TBI 12 Gy 1 Bu/Cy 3 RIC/NMA 29 Flu/Bu/ALG 10 Flu/TBI 2 Gy 10  Flu/TBI 2 Gy 5  Cy/Flu/TBI 2 Gy 4  AraC/Flu/TBI 2 Gy 1 Sequential 5  Amsa/AraC/Flu/Cy/Bu/ALG 3  Amsa/AraC/Flu/Cy/TBI 2 Gy/ALG 1  Amsa/AraC/Flu/Bu/ALG 1 Flu/Bu/Thiotepa/ALG 1 Flu/Mel 1 Cy/TBI 8 Gy 1 TLI/ALG 1 Figure 1. Cumulative incidences of relapse and non-relapse mortality Figure 1. Cumulative incidences of relapse and non-relapse mortality Figure 2. Non-relapse mortality according to donor type Figure 2. Non-relapse mortality according to donor type Disclosures No relevant conflicts of interest to declare.

scholarly journals AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR HIGH-RISK ACUTE LYMPHOBLASTIC LEUKEMIA: NON-RANDOMIZED STUDY WITH A MAXIMUM FOLLOW-UP OF MORE THAN 22 YEARS

2014 ◽  
Vol 6 (1) ◽  
pp. e2014047 ◽  
Author(s):  
Grzegorz Helbig ◽  
Malgorzata Krawczyk-Kulis ◽  
Malgorzata Kopera ◽  
Krystyna Jagoda ◽  
Patrycja Rzepka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

Objective. To evaluate the efficacy and toxicity of autologous hematopoietic stem cell transplantation (AHSCT) for high-risk acute lymphoblastic leukemia (ALL). Material and methods. Overall, 128 high-risk ALL patients at a median age of 26 years (range 18-56 years) at diagnosis received AHSCT between 1991-2008. Induction treatment was anthracycline-based in all patients. Conditioning regimen consisted of CAV (cyclophosphamide, cytarabine, etoposide) in 125 patients whereas 3 subjects received cyclophosphamide and TBI (total body irridation). Bone marrow was stored for 72 hours in 4oC and re-infused 24 hours after conditioning completion. Bone marrow was a source of stem cells in 119 patients, peripheral blood in 2 and 7 subjects received both bone marrow and peripheral blood. Results. With a median follow-up after AHSCT of 1.6 years (range 0.1-22.3 years), the probability of leukemia-free survival (LFS) for the whole group at 10 years was 27% and 23% at 20 years. Transplant-related mortality at 100 days after AHSCT was 3.2%.. There was a strong tendency for better LFS for MRD-negative patients if compared with patients who had positive or unknown MRD status at AHSCT (32% vs 23% and 25%, respectively; p=0.06). There was no difference in LFS between B- and T-lineage ALL as well as between patients transplanted in first complete remission (CR1) and CR2. LFS at 10 years for patients with detectable BCR-ABL at transplant was 20% and this was comparable with subjects with negative and missing BCR-ABL status (26% and 28%; p=0.97). Conclusions. The results of AHSCT for high-risk ALL remains unsatisfactory with low probability of long-term LFS.

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<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.

Allogeneic Hematopoietic Stem Cell Donation—Current Status with Regard to Safety

2011 ◽  
Vol 07 (02) ◽  
pp. 153
Author(s):  
Alberto Bosi ◽  
Benedetta Bartolozzi ◽  
◽  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
First Choice ◽  
Donation Process ◽  
Blood Stem Cells

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the first choice of treatment or an important therapeutic option for numerous diseases. Several stem cell sources, such as bone marrow, mobilized peripheral blood stem cells, and umbilical cord blood, are suitable for HSCT in clinical practice. However, this procedure is strongly related to availability of a histocompatible donor. In order to increase the probability of finding a histocompatible donor, national and international registries have been developed. Voluntary donation of bone marrow or peripheral blood stem cells for HSCT, both in the related or unrelated setting, is a well-established procedure with an invaluable ethical significance. Even if both procedures are safe, they are not risk free; therefore, the greatest attention has to be paid to the donor and to the donation process through a careful monitoring protocol for donor safety.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation for Therapy-Related Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2542-2542
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Jeremy Monfray ◽  
Hélène Labussière-Wallet ◽  
Sandrine Hayette ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Early Death ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells

Abstract Background: With the expanding pool of cancer survivors, therapy-related AML (t-AML) is increasingly encountered and constitutes approximately 10%-20% of newly diagnosed patients with AML. These patients have a poor prognosis with conventional anti-leukemia therapies with median survival of less than 1 year. This outcome is related to several factors including older age, worse performance score, comorbidities, therapy resistance, and bone marrow failure. Allogeneic hematopoietic stem cell transplantation, when feasible, represents a potential promising treatment for patients with t-AML. Objective: The aim of this study is to evaluate the different treatment options and outcomes of patients with t-AML followed at our center between year 2007 and 2013. Patients and methods: Between July 2007 and September 2013, we evaluated 166 consecutive newly diagnosed t-AML patients among a total of 572 AML diagnosed and followed in our center during this period; there were 95 (57%) males and 71 (43%) females with a median age of 66 years (range: 18-92), 48 (29%) were less than 60 years old, 83 (50%) were between 60 and 75 years, and 35 (21%) were older than 75 years; 128 (77%) were secondary AML after hematological malignancies [66 (56%) myelodysplastic syndrome (MDS) and 44 (34%) myeloproliferative syndromes and 18 (14%) lymphoid malignancies], and 38 (23%) after solid tumors. At diagnosis, the patients were evaluated according to both cytogenetic and molecular biology data as proposed by the European LeukemiaNet (Dohner et al. Blood 2010), accordingly, 160 (96%) patients were unfavorable [having one or more of the following: -5, -7, 5q-, 7q-,11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype (≥ 3 abnormalities), 3q26 abnormalities or EVI-1+], and only 6 (4%) had favorable prognosis [t(8;21), in(16) or t(16;16)]. Following the Acute Leukemia French Association (ALFA) guidelines for allo-HSCT in AML, all patients in this study should be candidate for transplantation after induction chemotherapy because of t-AML only if the patient condition is suitable (age, co-morbidities) and hematopoietic stem cell donor is available. Results: Among 166 patients, only 42 (25%) have been treated according to the ALFA recommendations and received induction chemotherapy followed by allo-HSCT, 36 (86%) were in first complete remission (CR1) and 6 were in less than CR1, 18 (43%) received hematopoietic stem cells from identical siblings (15 peripheral blood stem cells, 3 bone marrow) and 24 (57%) from unrelated donors (16 peripheral blood stem cells, 3 bone marrow and 5 cord blood cells); 31 (74%) received reduced intensity conditioning, 6 (14%) myeloablative and 5 (12%) sequential chemotherapy conditioning. For the rest of 124 (75%) patients, they could not benefit from allo-HSCT, they received either induction chemotherapy ± consolidation treatment or chemo/palliative treatment, among them 91 (73%) were ineligible to allo-HSCT due to age > 65 years and 33 (27%) could not be transplanted due to either non-availability of stem cells donor (N=12), early death before donor search (N=6), early death despite availability of stem cells donor (N=8), other comorbidities (N=7). The probability of overall survival (OS) at 2 years was 55% (range: 47-63) for patients who received allo-HSCT and it was 18% (range: 14-22) for those who received induction or palliative treatment without allo-HSCT with a median OS of 33 and 7 months respectively. The probability of progression-free survival for patients who received allo-HSCT was 68% (range: 60-76) at two years with a median not reached, and the cumulative incidence of transplant-related mortality was 24% (range: 17-31) at two years. Conclusion: Therapy-related acute myeloid leukemia remains having a poor prognosis with conventional therapy. Allogeneic HCT represents the only curative approach. We obtained encouraging results in eligible patients who received allogeneic transplantation especially that the majority of patients had unfavorable prognosis factors according to molecular biology and cytogenetics. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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