Risk Factors for Outcome after Haploidentical Hematopoietic Stem Cell Transplant in Children with Very High Risk Acute Lymphoblastic Leukemia: Impact of Centre Experience. A Survey on Behalf of the ALWP and PDWP of the EBMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 438-438 ◽  
Author(s):  
Thomas Klingebiel ◽  
Jacqueline Cornish ◽  
Myriam Labopin ◽  
Franco Locatelli ◽  
Adriana Balduzzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Alternative Option ◽  
Significant Difference ◽  
Very High

Abstract In the absence of an HLA identical donor, T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is an alternative option to treat children with very high risk acute lymphoblastic leukemia (ALL). However, little data is available in children. We have analyzed 118 children (≤16 years old) with ALL transplanted with a myeloablative Haplo-HSCT from 1995 to 2004 in Europe. Only transplants with 2 or more HLA disparities out of 6 (A, B and DRB1) were included. The median age was 8.5 years and median follow-up 56 months (8–116). At transplant, 21 (18%) were in CR1, 72 (61%) in CR2 or CR3 and 25 (21%) in more advanced phase. The 3-year leukemia free survival was 32±10%, 28±5% and 0%, respectively. Therefore we restricted the analysis to patients in remission (n=93) transplanted in 30 EBMT centers. Thirty-four (37%) patients were treated in centres performing more than 10 Haplo-HSCT in the study period (3 centres). The median age of recipient and donor was 8.7 and 37 years, respectively. Fifty four (65%) received a full Haplo-HSCT and 95% of the donors were parental. Twenty seven (29%) had t(9;21) or t(4;11). The majority of patients did not receive drugs for GVHD prophylaxis, ATG/ALG was used in conditioning in 74%, and 73% received TBI. The Clinimacs® device was used in 74% of selections. The median number of CD34+ cells infused was 12.8 106/Kg. Cumulative incidence with competing risk and KM estimates were used to calculate outcome probabilities. The median days of neutrophil recovery was 15 days (8–55) and 90% of patients had signs of engraftment. Acute GVHD II–IV was observed in 24% of the patients. In univariate analysis for LFS there was a trend towards better results for patients receiving higher CD34 cell dose (p=0.08) and a significant difference for patients transplanted in centres performing more Haplo-HSCT (49% versus 17%, p=0.002). Relapse incidence (RI) and non relapse mortality NRM) tended to be different between the experienced and less experienced centres. In less experienced centres NRM was 41% vs 27% (p=0.13) and RI 41% vs. 24% (p=0.10). There were patient, donor and transplant related differences between less and more experienced centres, specifically related to donor sex, Philadelphia positivity, year of transplantation, use of TBI, ATG and DLI and previous autograft. In conclusion, Haplo-HSCT is an alternative option to treat children with very high risk ALL in the absence of HLA identical donor. Centres with more experience have better LFS.

Molecular Relapse of Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation Can Be Successfully Treated with Donor Lymphocyte Infusions.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5122-5122
Author(s):  
Alida Dominietto ◽  
Anna Maria Raiola ◽  
Raffaella Grasso ◽  
Anna Garuti ◽  
Carmen di Grazia ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Donor Lymphocyte Infusions

Abstract Background. Hematologic relapse is seen in 20–40% of adult acute lymphoblastic leukemia (ALL) patients undergoing an allogeneic hematopoietic stem cell transplant (HSCT) and is usually non responsive to donor lymphocyte infusions (DLI). This has suggested a lack of graft vs leukemia effect (GvL) in ALL patients. It is currently possible to monitor minimal residual disease (MRD) post-HSCT and this may allow to identify patients at high risk of hematological relapse. Objectives. To monitor MRD in B-ALL patients post-HSCT and to treat MRD positive patients with DLI. Patients and Methods. MRD was evaluated on bone marrow samples using nested polymerase chain reaction (PCR) and real time PCR (RT-PCR) assay to analyze respectively IgH VDJ and BCR-ABL gene rearrangement. Molecular positivity/relapse was defined with two consecutive positive PCR assays. MRD monitoring was performed in 28 patients grafted from an HLA-identical sibling (n=19), family mismatched related donor (n=2) or matched unrelated donor (n=7). Median follow-up was 47 months (range 5–163). Sixteen patients (57%) were in early disease phase at the time of transplant. Results. We identified 3 groups of patients. A) 14 patients (50%) had no evidence of MRD after HSCT. B) 6 (21%) had a positive MRD and received escalating dose DLI, within 60 days and C) 8 (29%) had a positive MRD, but did not received DLI, because not available or because of an early hematological relapse. Median time from HSCT to molecular relapse was 139 days (range 46–1048). The median follow up was 1385 days (144 – 4877). Median number of infused CD3+ cells was 0.6x10^7/Kg of recipient body weight (range 0.01–7). Hematological relapse was seen in 0%, 0% and 88% respectively of group A,B,C (p=0.0001) and disease-free survival (DFS) was 100% , 67% , 12% (p=0.0001). Conclusions. This study shows that (1) MRD monitoring of ALL patients post-transplant identifies patients at high risk of hematologic relapse and (2) that treatment with DLI, on the basis of MRD positivity, significantly reduces the risk of leukemia relapse and may improve DFS. These data also confirm the existence of a GvL effect, previously shown in this disease (Weiden et.al NEJM, 300, 1068; 1979).

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)–rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2644-2650 ◽  
Author(s):  
Georg Mann ◽  
Andishe Attarbaschi ◽  
Martin Schrappe ◽  
Paola De Lorenzo ◽  
Christina Peters ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Mixed Lineage Leukemia ◽  
Hematopoietic Stem ◽  
Significant Difference

AbstractTo define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL+), we compared the outcome of MLL+ patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL+. Among the 277 of 297 MLL+ patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 297 MLL+ patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL+ acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487.

Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group

Blood ◽  
2010 ◽  
Vol 115 (17) ◽  
pp. 3437-3446 ◽  
Author(s):  
Thomas Klingebiel ◽  
Jacqueline Cornish ◽  
Myriam Labopin ◽  
Franco Locatelli ◽  
Philippe Darbyshire ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Very High

Abstract T cell–depleted haploidentical hematopoietic stem cell transplantation (haploHSCT) is an option to treat children with very high-risk acute lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127 children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or third (n = 32), complete remission or in relapse (n = 25). The 5-year leukemia-free survival (LFS) was 30%, 34%, 22%, and 0%, respectively. A risk-factor analysis was performed for patients who underwent transplantation in remission (n = 102). Five-year nonrelapse mortality (NRM), relapse incidence (RI), and LFS were 37%, 36%, and 27%, respectively. A trend of improved LFS rate and decreased RI was observed for children given a graft with higher number of CD34+ cells (adjusted P = .09 and P = .07, respectively). In a multivariate analysis, haploHSCT performed in larger centers (performing ≥ 231 allotransplantations in the studied period) was associated with improved LFS rate and decreased RI (adjusted P = .01 and P = .04, respectively), adjusting for different patient-, disease-, and transplant-related factors such as number of previous autotransplantations, cytomegalovirus serology status, type of T-cell depletion, and use of total body irradiation and antithymocyte globulin. In conclusion, higher CD34+ cell dose and better patient selection may improve outcomes of children with ALL who undergo a haploHSCT. Transplant centers initiating programs on haploHSCT for children may collaborate with more experienced centers.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukemia: Shifting Indications in the Era of Immunotherapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Tony H. Truong ◽  
Cristian Jinca ◽  
Georg Mann ◽  
Smaranda Arghirescu ◽  
Jochen Buechner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Poor Response ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Hematopoietic Stem

Pediatric acute lymphoblastic leukemia generally carries a good prognosis, and most children will be cured and become long-term survivors. However, a portion of children will harbor high-risk features at the time of diagnosis, have a poor response to upfront therapy, or suffer relapse necessitating more intensive therapy, which may include allogeneic hematopoietic stem cell transplant (HSCT). Recent advances in risk stratification, improved detection and incorporation of minimal residual disease (MRD), and intensification of upfront treatment have changed the indications for HSCT over time. For children in first complete remission, HSCT is generally reserved for those with the highest risk of relapse. These include patients with unfavorable features/cytogenetics who also have a poor response to induction and consolidation chemotherapy, usually reflected by residual blasts after prednisone or by detectable MRD at pre-defined time points. In the relapsed setting, children with first relapse of B-cell ALL are further stratified for HSCT depending on the time and site of relapse, while all patients with T-cell ALL are generally consolidated with HSCT. Alternatives to HSCT have also emerged over the last decade including immunotherapy and chimeric antigen receptor (CAR) T-cell therapy. These novel agents may spare toxicity while attempting to achieve MRD-negative remission in the most refractory cases and serve as a bridge to HSCT. In some situations, these emerging therapies can indeed be curative for some children with relapsed or resistant disease, thus, obviating the need for HSCT. In this review, we seek to summarize the role of HSCT in the current era of immunotherapy.

Which Patients with Adult Acute Lymphoblastic Leukemia Should Undergo a Hematopoietic Stem Cell Transplantation? Case-Based Discussion

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 444-452 ◽  
Author(s):  
Hillard M. Lazarus ◽  
Selina Luger
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

AbstractThe decision to proceed to transplant for adult patients with acute lymphoblastic leukemia (ALL) is not clear-cut. Relapse and nonrelapse mortality continue to plague the outcome of hematopoietic stem cell transplantation (HSCT) even when undertaken in complete remission (CR). Those considered to be at high risk for relapse often are considered for HSCT in first complete remission (CR1) while those at lower risk may not be referred until they have relapsed, when their chances for cure are very poor. In some patients who have a suitable histocompatible sibling, disease- or patient-related factors may override the potential benefit of allogeneic HSCT. Because many patients do not have a suitable histocompatible sibling, one has to consider the relative merits of autologous transplantation versus use of an alternative allogeneic stem cell source, such as a matched-unrelated donor (MUD), umbilical cord blood (UCB) donor, or haploidentical donor. Deciding among these options in comparison to chemotherapy even in high-risk patients is difficult. In the review, the risks and benefits of these choices are discussed to determine whether and by what means to proceed to HSCT in adult patients with ALL who are in CR1. Presented are two patients with ALL and a discussion of how the data we provide would lead to a decision about the selection of therapy.

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