Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in the Treatment of Acute Lymphocytic Leukemia (ALL) in 126 Adults: Impact of Donor Source on Leukemia Free Survival (LFS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2064-2064 ◽  
Author(s):  
Priya Kumar ◽  
Todd E. Defor ◽  
Claudio Brunstein ◽  
Juliet Barker ◽  
John E. Wagner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Growth Factor ◽  
Disease Status ◽  
Lymphocytic Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Cell Source ◽  
Donor Source

Abstract White blood cell (WBC) count and specific cytogenetic abnormalities at diagnosis, patient age and disease status at HSCT have previously been identified as risk factors associated with LFS in patients with ALL. As the use of umbilical cord blood (UCB) is relatively new, particularly for adults, we sought to evaluate the relative impact of donor source. In this single center study, 126 adults aged 18–61 (median 31) years (yrs) underwent myeloablative conditioning (cyclophosphamide 120 mg/kg and total body irradiation 1320–1375 cGy based regimen in 92%) followed by allogeneic HSCT. Stem cell source was an HLA matched related donor (MRD) in 85, HLA matched unrelated donor (URD:M) in 15, HLA mismatched unrelated donor (URD:MM) in 14 and HLA 0–2 (A, B, DRB1) mismatched UCB in 12. At the time of HSCT, 64 patients were in CR1, 51 in CR2, and 11 patients in ≥ CR3; 20 pts had T-lineage disease; 38 pts (30%) had either t(9;22)(n=28), t(4;11) or t(1,19) (n=10) with the remainder (70%) having normal cytogenetics. WBC ≥ 30 x 109/l at diagnosis was documented in 50%. Demographics, disease characteristics at initial diagnosis and transplant variables were similar in all 4 groups except: year of transplant after 1996 and use of growth factor for all UCB recipients. Outcomes by donor source: MRD URD:M URD:MM UCB P N 85 15 14 12 Median follow up in yrs 9.3 3.5 7.2 1.2 OS 1 yr % (95% CI) 41 (31–52) 33 (9–57) 14 (0–33) 75 (51–100) 0.02 LFS 1 yr % (95% CI) 35 (25–45) 27 (4–49) 14 (0–33) 67 (40–93) 0.03 Relapse 1 yr % (95% CI) 21 (12–30) 20 (0–40) 0 8 (0–23) 0.22 TRM 1 yr % (95% CI) 44 (33–55) 53 (27–79) 86 (57–100) 25 (1–49) <0.01 As a consequence of low TRM, OS and LFS were superior after UCB transplants. In multiple regression analysis, 5 independent risk factors were significantly associated with poorer OS: use of URD:M (RR 3.8, 95% CI 1.1–13.8, p= 0.04) and URD:MM (RR 4.9, 95% CI, 1.3–19.1, p= 0.02), ≥ CR3 at HSCT (RR 3.0, 95% CI, 1.1–8.8, p= 0.04), WBC >30 x 109/l (RR 2.4, 95% CI, 1.4–4.1, p<0.01), cytomegalovirus (CMV) seropositive recipient and donor (RR 4.0, 95% CI, 2.0–7.9, p<0.01), and ≥ 2 induction regimens to achieve initial CR (RR 2.7, 95% CI, 1.2–5.9, p= 0.01). Patients who developed grade II–IV acute graft versus host disease (GVHD) had significantly lower mortality rates (RR 0.4, 95% CI, 0.2–0.7, p<0.01). There was no impact on OS by year of transplant or use of growth factor. Variables associated with poor LFS were identical to those for OS, and GVHD was again associated with improved LFS. These results support the use of UCB as an alternative stem cell source for adults with ALL with results comparable to outcomes observed with MRDs. In addition, GVHD is associated with improved LFS suggesting a significant graft versus leukemia effect with all donor graft sources.

Risk Factors for 30-Day Hospital Readmission Following Myeloablative Allogeneic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1532-1532
Author(s):  
Nelli Bejanyan ◽  
Aleksandr Lazaryan ◽  
Lisa Rybicki ◽  
Shawnda Tench ◽  
Steven Andresen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hospital Readmission ◽  
Unrelated Donor ◽  
Day Hospital ◽  
Stem Cell Source ◽  
Cell Source ◽  
Preparative Regimen

Abstract Abstract 1532 Introduction: Patient readmission within 30 days from discharge has been perceived by Centers for Medicare and Medical Services as an indicator of poor health-care quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic stem cell transplantation (AlloHSCT) were previously found to have higher rates of readmission as compared to those with autologous HSCT. The purpose of this exploratory retrospective study was to identify the reasons and risk factors for 30-days readmission among the recipients of myeloablative AlloHSCT. Methods: 618 adults were at risk for 30-day readmission following AlloHSCT from 1990 to 2009 at our single academic institution. Recursive partitioning analysis was used to identify the most optimal grouping of various preparative regimens relative to readmission. Univariate and multivariable risk factors for readmission were identified with logistic regression analysis. Impact of 30-day readmission on overall mortality was estimated by Cox proportional hazards analysis. Results: 242 (39%) of 618 patients (median age=42 years [range, 18–66]; 54% males; 89% Caucasians) were readmitted after a median of 10 days (range, 1–30) from discharge. Median duration of readmission was 8 days (range, 0–103). Infections (n=68), fever without identified source of infection (n=63), gastrointestinal complications (n=44), GVHD (n=38), and other reasons (n=29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. 30% of readmitted patients had lymphoid and 67% had myeloid malignancy; 90% received ≥1 prior chemotherapy; 26% had TBI-containing preparative regimen; bone marrow was the most common (84%) source of stem cells; 46% had unrelated donor AlloHCST. During their index admission, 65% of subsequently readmitted patients were hospitalized for more than 29 days; 52% of patients recovered their ANC > 500/mL within 15 days; 41% had infection; 16% had grade II-IV GVHD. In univariate analysis, greater risk for readmission was associated with lymphoid malignancy (vs. myeloid, p=0.03), more previous chemotherapy regimens (p=0.01), TBI-containing preparative regimen (p<0.001), peripheral stem cell source (vs. bone marrow, p=0.01), unrelated donor (p<0.001), and infection during admission for AlloHSCT (p<0.001). In multivariable analysis, TBI-based preparative regimen (HR=2.6; 95% CI, 1.6–4.2), infection during admission for AlloHSCT (HR=2.3; 95% CI, 1.6–3.3), and peripheral stem cell source (vs. bone marrow, HR=1.9; 95% CI, 1.03–3.4) predicted 30-day readmission. 30-day readmission was an independent predictor of all-cause mortality (HRAdj=1.8; 95% CI, 1.5–2.2). Conclusion: 30-day hospital readmissions following myeloablative AlloHSCT portended poor survival. Our data emphasize the importance of risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation. Further studies will be necessary to validate our findings. Disclosures: No relevant conflicts of interest to declare.

Influence of Stem Cell Source On GvH and NRM: Comparison of 10/10 HLA-Matched Unrelated Donor (MUD) with 9/10 HLA-Mismatched Unrelated Donor (MMUD) and Unrelated Cord Blood (UCB) Transplants.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3135-3135
Author(s):  
Clémence Granier ◽  
Emeline Masson ◽  
Lucie Biard ◽  
Raphael Porcher ◽  
Regis Peffault de la Tour ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source

Abstract Abstract 3135 Background: When an HLA-matched donor is not available for allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the use of an alternative HLA-mismatched stem cell source may be considered. In Europe, HLA compatibility for HSCT is calculated for 10 alleles (HLA-A, -B, -C, -DRB1, -DQB1). The aim of this study was to retrospectively compare outcomes after transplantation from 10/10 HLA-MUD, 9/10 HLA-MMUD and UCB performed at the Hospital Saint Louis (Paris, Fr). Methods: Patients receiving a first allogeneic transplantation from a 10/10, 9/10 UD or UCB from 2000 to 2011 were included. High resolution HLA typing was performed by PCR SSO and SSP for HLA loci: A, B, C, DRB1 and DQB1. The following variables were studied as risk factors for transplant outcomes: disease, disease risk (standard/high risk), age at transplant, gender, donor/recipient sex-matching, ABO matching, donor/recipient CMV status, conditioning regimen, and use of anti-thymoglobulin (ATG). Results: 355 consecutive patients with hematologic malignancies were analyzed. One hundred and ninety-six were transplanted with MUD, 84 with MMUD (mismatches for HLA-A: 16%, -B: 16%, -C: 39%, -DRB1: 8%, -DQB1: 21%) and 75 with UCB (52% with single and 48% with two UCB unit; 87% of all UCB transplants were 4–6/6 HLA-matched). Median patient age was 31 (range: 5–55). Patient characteristics differed between the 3 groups: (i) median age at transplant: 36 in MUD, 31 in MMUD, 22 in UCB (p<0.0001), (ii) high risk disease: 37%, 51%, 68% (p<0.0001), (iii) CMV negative donor/positive recipient: 31%, 36%, 60% (p<0.0001), (iv) use of ATG: 37%, 64%, 55% (p<0.0001). Cumulative incidences of grade II-IV and grade III-IV acute GvHD disease (aGvHD) were 61% (66% for MUD, 60% for MMUD and 48% for UCB) and 17% (17%, 24% and 15%), respectively. Three-year cumulative incidence of chronic GvHD (cGvHD) was 46% (51% for MUD, 49% for MMUD and 29% for UCB). Three-year NRM was 34% (28% for MUD, 31% for MMUD and 51% for UCB). Graft failure occurred in 15% of UCB patient, 8% in MMUD group and 3% in MUD group (significant difference between UCB and MUD: OR=5.44, 95%CI 1.93–15.3, p=0.001). Multivariate analysis is summarized in table 1. It showed that MMUD tented to have a higher incidence of aGvHD III-IV than MUD and UCB. UCB had a lower incidence of cGvHD than MMUD. No significant effect of HSCT source on NRM was demonstrated. Conclusion: Compared to MMUD, UCB-HSCT induces less cGvHD and non significantly increased NRM. Compared to MUD, MMUD and UCB-HSCT did not result in a clear increase of NRM. UCB and 9/10 HLA-MMUD are both suitable stem cell sources for patients who cannot benefit from 10/10 HLA-MUD transplant. Disclosures: No relevant conflicts of interest to declare.

HLA-DRB4 Mismatch Is Associated with Worse Outcomes in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4540-4540 ◽  
Author(s):  
Marie Y. Detrait ◽  
Ibrahim Yakoub-Agha ◽  
Valerie Dubois ◽  
Françoise Dufossé ◽  
Myriam Labalette ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Stem Cell Source ◽  
Cell Source

Abstract Abstract 4540 Introduction The impact of HLA DRB3 and DRB4 allele mismatch after allogeneic HSCT using unrelated donors is unclear. We therefore examined retrospectively the outcome of 35 patients who received HLA-10/10 unrelated hematopoietic stem cell transplantation with a DRB3 or DRB4 mismatch between 2005 and 2011. This cohort of 35 patients was a part of a cohort of 132 consecutive patients who underwent allogeneic HSCT between 2005–2011 with a 10/10-HLA matched donor. There were 18 males (51.4%) and 17 females (48.6%) with a median age of 48 years (range, 6–64), there were 13 (37%) AML, 9 (26%) ALL, 4 (11.5%) MDS, 3 (8.5%) multiple myeloma and 6 (5.7%) other (CML, CLL, NHL). Twenty patients (57%) received a myeloablative conditioning (MAC) and 15 (43%) received a reduced intensity conditioning (RIC). At transplantation, 21 patients (60%) were in complete remission (CR), 4 patients (11.5%) in partial remission (PR) and 10 (28.5%) in relapse; 13 (37%) patients received peripheral blood stem cell (PBSC) and 22 (63%) received bone marrow (BM). Twelve (34%) patients had a mismatched DRB4 donor and 23 (66%) patients had a mismatched DRB3 donor. In the remains of 97 patients, there were 55 male (57%) and 42 female (43%), 28 (29%) patients received a MAC and 69 (71%) a RIC as regimen before allogeneic HSCT. The stem cell source was BM for 32 (34%) patients and PBSC for 65 (66%). At transplantation, 34 (35%) patients are in CR and 63 (65%) were in PR. The distribution of diagnosis was acute leukaemia and MDS for 44 (45%), CLL for 2 (2.5%) and other diagnosis (aplastic anemia, NHL, CML, MPS) for 51 patients (52.5%). Results After HSCT, 124 (94%) patients engrafted. After a median follow-up of 11.5 months (range, 0–76), the cumulative incidence of acute GvHD≥2 at 3 months was 20% (95%CI,16.5–24) and the cumulative incidence of chronic GvHD at one year was 19 % (95%CI, 15–22). In univariate analysis, the mismatch DRB3 or DRB4 had no effect on engraftment and no effect on acute GvHD (p=0.08) or chronic GvHD (p=0.63). There was no impact of DRB3 or DRB4 mismatch on relapse (p=0.33 and p=0.53, respectively) and on PFS (p=0.63 and p=0.07, respectively). We found an impact of the DRB4 mismatching (p=0.016) on overall survival. The median survival for patient without DRB3 or DRB4 mismatch was 23 months (14-NR), for patients with DRB3 mismatch 32 months (12-NR), and for DRB4 mismatched patients 5 months (3-NR). The probability of survival at 24 months, for patients without mismatch DRB3 or DRB4 is 47% (36–61), for patients with DRB3 mismatch 51% (32–82) and for DRB4 mismatched patients 19% (6–66%). (figure1). The multivariate analysis that studied age, type of disease, DRB3 or DRB4 mismatch, sexmatching, TBI, ATG, disease status at transplantation and type of conditioning and stem cell source showed a significant impact of mismatch DRB4 on survival (HR= 2.5 [95%CI, 1.2–5.5] p=0.019); there was no impact for DRB3 mismatch (HR= 1.3 (95%CI,0.5–3.9 p=0.58). We found also an impact of the DRB4 mismatch on TRM (HR= 3.5; [95%CI, 1.6 –8] p= 0.026). The incidence of TRM at 24 months for patients without DRB3 or DRB4 mismatch is 29% (24–34), for patients with DRB3 mismatch 17% (9–26%) and for DRB4 mismatched patients 50% (34–66%). (figure 2). Conclusion The HLA DRB4 matching donor is relevant for survival of patients who undergo allo-HSCT from unrelated donor in the HLA-10/10 matching settings. In view of the important impact of these loci mismatches on clinical outcome, it seems to be important to consider this matching loci in the unrelated donor selection. Disclosures: No relevant conflicts of interest to declare.

Higher Cell Dose and CD34+ Content Improves Engraftment Following Unrelated Donor Cord Blood Transplantation (CBT): A Report of the National Marrow Donor Program (NMDP) Cord Blood (CB) Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 975-975 ◽  
Author(s):  
Donna Wall ◽  
John Wagner ◽  
Mary Laughlin ◽  
Karen Ballen ◽  
Susan Staba ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Cell Count ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
Stem Cell Source ◽  
Cell Source ◽  
Recipient Age ◽  
The Impact

Abstract Cord blood has become an important alternative unrelated donor allogeneic hematopoietic stem cell source. The NMDP has developed a comprehensive coordinated network of CB banks, search coordinating center and transplant programs with prospective collection of outcome data coordinated by the NMDP (now CIBMTR). Critical to CBT has been limited cell dose with resultant prolonged engraftment time. The NMDP cord blood inventory has both total nucleated cell count (TNC) and CD34+ quantification on the units, allowing a comparison of the relative utility of either measure in identifying units that would result in rapid engraftment. We report a retrospective review of the NMDP CBT experience, analyzing the impact of graft characteristics with engraftment and survival. Between 03/2000 and 03/2004, 12 NMDP banks (total inventory 31,976 units) released CB units to 144 patients at 44 NMDP transplant programs included in this analysis (median f/u 217 days, 26–1204 days). The median recipient age was 8.2 years (0.2–63.1 years, 38 were ≥ 15 years) and median weight was 27 kg (3–158 kg: 26% > 57 kg). Transplant indications included malignancy in 113 (ALL 36, AML 43, MDS 13, other 21), metabolic disorders (8) immune disorders (9) histiocytic disorders (3), erythrocytic abnormalities (6), platelet abnormality (1), SAA (3) and other nonmalignant disease (1). Most malignancy patients had advanced disease (60 patients (53%) were beyond CR2 or in relapse). The median prefreeze TNC was 4.4 x 107/kg (0.3–433 x 107/kg) and CD34+ cells 7.9 x 105/kg (1.1–68.5 x 105/kg) in units selected for transplantation. Thus the median CB TNC was 142 x 107 cells (54–396 x 107 cells); only 12 units under 80 x 107 cells were used. 114 patients engrafted by day +42 post CBT with median time to neutrophil recovery > 500/mm3 of 21 days (8–62 days) and platelet count > 20,000 x 109/L of 64 days (12–473) respectively. 1-year survival and DFS were 39% ± 9% and 38% ± 9% respectively. Relapse rate was 16% ± 8% in this high risk population. The 100-day TRM rate was 26% ± 7%. For patients > 15 yrs, TRM was 42% ± 16% vs. 21% ± 8% for patients < 15 years. Higher cell dose was associated with faster neutrophil and platelet engraftment. Units with both high TNC/kg and high CD34+/kg were associated with more rapid engraftment vs. those with only high TNC or high CD34+ or neither (p<0.0001). In multivariate analysis, recipient age > 15 years led to poorer survival (RR 3.4 (1.7, 6.7)) and DFS (RR 2.8 (1.5, 5.2)) compared to younger children, especially those < 3 years (p<0.0001). Male grafts into females yielded poorer survival than other gender combinations. These data confirm that CB is a valuable alternative unrelated donor histocompatible stem cell source. Since transplantation using CB units containing both high TNC and CD34+ content resulted in more rapid engraftment, optimal CB inventory should strive for both high cell count (> 80 x 107 cells) and high CD34+ cell content.

Donor Stem Cell Source Does Not Impact Outcome of High Risk (HR) Acute Myeloblastic Leukaemia (AML) Patients After Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation (RIC-ALLO).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4339-4339
Author(s):  
Sabine Furst ◽  
Luca Castagna ◽  
Thomas Prébet ◽  
Claude Lemarie ◽  
Jean El Cheikh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Unrelated Donor ◽  
Special Focus ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source ◽  
Donor Type

Abstract Abstract 4339 Allogeneic Stem Cell Transplantation (ASCT) offers a potential curative treatment approach of HR AML patients (pts). Over years, the use of umbilical cord blood (UCB) has become an attractive alternative stem cell source for those pts lacking a suitable HLA matched related or unrelated donor. The aim of this analysis was to assess the outcome of 50 pts who received a RIC-ALLO in our centre between 2005 and 2008 with a special focus on three different donor sources: identical sibling, unrelated donor or UCB. All pts had HR AML in complete remission (CR) at time of transplant. HR features were defined as at least one of the following criteria: CR1 with unfavourable cytogenetics, secondary AML, more than one induction chemotherapy for obtaining CR or CR2 and above. Reasons for RIC regimen were older age, unfit physical condition, comorbidities or prior autologous transplant. All pts received a Fludarabine-based RIC regimen with GVHD prophylaxis consisting in CSA alone or CSA and MMF. The median age of all pts was 51 (range, 19-70) years. 28 pts had identical sibling donors, 7 pts had a matched 10/10 (5 pt) or mismatched 9/10 (2 pt) unrelated donors and 15 pt received a single or double UCBT. Pts characteristics were comparable between the three groups but for pt age [identical sibling group: 52 (range, 35-70) years; unrelated donor group: 61 (range, 50-66) years; UCB group: 44 (range, 19-61) years]. After a median follow-up of 886 (range, 336-1528) days, 20 pts have died (disease=6, treatment related=14) and 8 pts have experienced relapse. Four year OS and EFS for all pts were 57% and 54%, respectively with no significant difference between the 3 groups (2 year OS: 61%, 54% and 66%; 2 year EFS: 59%, 54% and 45% respectively). One year TRM was 20% for the entire group and did not significantly differ between the 3 groups. Despite the obvious limitations of this small series, results seem to indicate that in this population, donor type does not highly influence outcome. This is quite encouraging as most of the pts lack a compatible sibling donor. This may invite to consider privileging a rapid identification of an alternative donor rather than a given donor type when a match sibling is not available. Thus concomitant search for both graft type should be undertaken in order to perform allo SCT in a larger number of pts otherwise not treated because of early progression as illustrated in the underrepresentation of alternative transplant as compared with familial transplant in this retrospective study (28 familial vs 22 alternative). Disclosures: No relevant conflicts of interest to declare.

Risk Factors to Develop Sclerotic Chronic GvHD After Allogeneic HSCT: Preliminary Results of a Multicentre Retrospective study From the Société Française De Greffe De Moelle Et De Thérapie Cellulaire (SFGM-TC)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1947-1947
Author(s):  
Marie Y. Detrait ◽  
Roberto Crocchiolo ◽  
Stephane Vigouroux ◽  
Jacques-Olivier Bay ◽  
Mohamad Sobh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Cord Blood ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Allogeneic Hsct ◽  
Factors Associated ◽  
Stem Cell Source ◽  
Cell Source ◽  
Unrelated Donors

Abstract Abstract 1947 Introduction Sclerotic cGvHD is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). The sclerotic skin manifestations of cGvHD result from inflammation and fibrosis of the dermis, subcutaneous tissue, or muscular fascia, leading to functional disability. Risk factors associated with sclerotic cGvHD remain not well studied. TBI, PBSC, female recipient, and prior severe skin acute GvHD were identified as factors associated with an increased risk of sclerotic cGvHD in a large previous retrospective study from Seattle (n=986 patients) which was presented at the ASH 2011 meeting. Objective In the aim to validate the previous risk factors in France, we have conducted this retrospective multicentric analysis. We present here the preliminary results from four centers, seven are expected in the next months. Between 2005 and 2010, 437 consecutive patients who received systemic therapy for chronic GvHD after a first allogeneic HSCT were included. Chronic GvHD was diagnosed by the NIH consensus criteria. Sclerotic GvHD was defined by manifestations of cutaneous sclerosis, fasciitis or joint contracture in the medical record. Analyses to determine risk factors included as variable patient and donor age, kind of donor, HLA matching, diagnosis, stem cell source, patient and donor gender, intensity of conditioning regimen, use of total body irradiation (TBI) or antithymocyte globulin (ATG) in the conditioning regimen, and prior acute GvHD. Results All patients had hematological malignancies, the median age is 45 (17–65), 227 patients (52%) had HLA-matched related donors, 125 (29%) had HLA-matched unrelated donors, 48 (11%) had HLA- 9/10 unrelated donors and 37 (8%) had one or two cord blood unit (HLA-4/6 or 5/6 matched). The median time from allogeneic HSCT to chronic GvHD was 6.5 (1.8–41.5) months; 69 patients (15.7%) presented sclerotic features at initial diagnosis or after the onset of chronic GvHD. The cumulative incidence of sclerotic cGvHD was 12% (95%CI, 11–13.5) at 5 years after onset of chronic GvHD (Figure). From the 69 patients who experienced sclerotic cGvHD, 49 patients (71%) had HLA-matched related donors, 19 patients (27.5%) had HLA-matched unrelated donors, and 1 patient (1.5%) had HLA-mismatched unrelated donor. In univariate analysis, we found more sclerotic cGvHD in patients who had multiple myeloma (p=0.018); this effect seems to be associated with the prophylaxis for GvHD with CsA alone. There was no effect of TBI or intensity of conditioning. There was more sclerotic GvHD in female recipient (p=0.032) and for patients who had an unrelated donor (p=0.0028). In multivariate analysis (Table), factors associated with an increased risk of sclerotic cGvHD were female recipient, patients with unrelated donor, and patients with previous aGvHD. Cord blood as stem cell source was associated with a lower risk of sclerotic GvHD. Prophylaxis of GvHD with CsA alone showed a trend to a higher risk. At the last follow-up, of the 69 patients, 51 (74%) were alive and 10 (14.5%) died from cGvHD. Conclusion In this intermediate analysis, we found that female recipient, unrelated donor, previous aGvHD are risk factors for developing sclerotic cGvHD. Moreover, we found that cord blood as stem cell source is a protector factor. Study of GvHD prophylaxis, ABO matching, type of HLA-mismatching, acute skin GvHD is ongoing on the whole cohort (n= 1587 patients from 7 centers) and results will be communicated later. After the final analysis on the whole cohort we would like to establish a score risk of sclerotic cGvHD in the goal to conduct a prospective study in France with a prophylactic treatment for high risk patients. Disclosures: No relevant conflicts of interest to declare.

Comparable Outcomes After Sibling and Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantations (HCT) In Adult Acute Lymphoblatic Leukemia (ALL) With First Complete Remission (CR)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2142-2142
Author(s):  
Betul Oran ◽  
Michelle Poon ◽  
Julianne Chen ◽  
Gabriela Rondon ◽  
Sairah Ahmed ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Board Of Directors ◽  
Disease Status ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Advisory Committees ◽  
Stem Cell Source ◽  
Cell Source ◽  
Donor Type

Abstract A landmark study from Medical Research Council/Eastern Cooperative Oncology Group showed improved survival (∼53%) for patients allocated to sibling HCT versus either consolidation/maintenance chemotherapy or autologous HCT. Matched unrelated donors (MUD) are an option for patients without a SIB available and we retrospectively analyzed disease outcomes after SIB and MUD in adult ALL patients. Between 2001and 2012, 204 adult ALL patients with a median age of 36 years (range, 18-64) were transplanted with a SIB (n=112) or 8/8 MUD (n=92). Disease status at HCT was first or second complete remission and beyond (CR1, n=113, 55.5% and CR2+, n=91, 44.5%). Conditioning was myeloablative in 177 (86.8%) and reduced intensity (RIC) in 27 patients (13.2%). All but 2 patients received graft versus host disease (GVHD) immunosuppression with tacrolimus and methotrexate. Patient and disease characteristics including age, sex, histological subtypes and high risk disease features (WBC and cytogenetic classification at diagnosis), disease status at HCT and conditioning intensity were similar between SIB and MUD recipients. As expected, MUD patients had bone marrow (BM) as the stem cell source more commonly than SIB (69.6% vs. 7.1, p&lt;0.001). The median follow-up of 96 survivors was 36 months. The univariate point estimates at the stated timepoints and multivariate outcomes are summarized in the Table1 and 2.Table1The summary outcomesSIB (%)MUD (%)PNeutrophil recovery at day 4296.497.80.6Platelet recovery at day 1009281.50.03Grade II-IV aGVHD30.248.30.0093 year TRM in CR124.628.70.63 year TRM in CR2+21.023.10.83 year relapse incidence in CR124.420.60.63 year relapse incidence in CR2+49.939.60.33 year OS in CR155.955.60.83 year OS in CR2+33.137.90.8Table 2Multivariate results for OS*HR95%CIPCR1RefCR21.71.1-2.50.01Age &lt;35RefAge&gt;=351.71.1-2.60.01*Adjusted for cytogenetics and WBC at diagnosis, donor type and conditioning intensity.Figure 1Overall survival by disease status and donor typeFigure 1. Overall survival by disease status and donor type In summary, hematopoietic transplantation using a MUD was associated with slower platelet recovery which could be due to more common use of BM as the stem cell source. Acute GVHD incidence was also higher with MUD transplants but OS was comparable between donor types, even when patients were transplanted in CR1. Thus, in the absence of a SIB donor, a matched unrelated donor is an acceptable donor source for HCT with comparable overall survival. Disclosures: Qazilbash: Celgene: Membership on an entity’s Board of Directors or advisory committees Other; Millenium: Membership on an entity’s Board of Directors or advisory committees, Membership on an entity’s Board of Directors or advisory committees Other.

scholarly journals Outcome of Hematopoietic Stem Cell Transplantation in the Patients with Pediatric Acute Lymphoblastic Leukemia Enrolled in the Japan Association of Childhood Leukemia Study (JACLS) ALL-02

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4605-4605
Author(s):  
Mio Yano ◽  
Hisashi Ishida ◽  
Yoshiko Hashii ◽  
Asahito Hama ◽  
Yoshiyuki Kosaka ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Cell Source

Background: Though the outcome of patients with acute lymphoblastic leukemia (ALL) has been greatly improved, some high-risk patients still need hematopoietic stem cell transplantation (HSCT). In this study, we evaluated clinical characteristics of children with ALL who were treated according to Japan Association of Childhood Leukemia Study (JACLS) ALL-02 trial and received HSCT to determine prognostic factors for the outcome of HSCT. Methods: Between April 1, 2002 and March 31, 2008, 1,252 patients aged 1-18 years with newly diagnosed ALL were enrolled in JACLS ALL-02 trial. Ph+ALL, mature B-ALL, and NK-leukemia were excluded. Of all the 1,252 patients, 211 (16.8%) patients were reported to receive HSCT, of which 206 patients with adequate information of 1st HSCT were subjected to further analysis. In this study, HSCT in 1st complete remission (CR) in JACLS ALL-02 trial was indicated for the patients with extremely high risk (ER: BCP-ALL with PPR and/or evidence of t(4;11) (or KMT2A-AFF1 positive), hypodiploidy (≤ 44) and/or acute mixed lineage leukemia/ acute unclassified leukemia). As a precaution, in ER patients, the timing of HSCT differs depending on whether they have a matched related donor. Results: Of all the 206 patients, 83 patients received HSCT in first CR (CR1), 68 patients in CR2, 54 patients in non-CR and 1 patient in induction failure (IF). 5-year overall survival (5y-OS) for 206 patients was 50% (95% CI 42.7-56.8). In detail, 73.8% (95% CI 62.6-82.1) for CR1 patients, 49.4% (95% CI 35.9-61.5) for CR2 patients, and 14.8% (95% CI 6.9-25.5) for non-CR patients, respectively. In univariate analysis, JACLS risk classification, disease status at HSCT (CR or non-CR or IF), stem cell source were significant prognostic factors. In multivariate analysis, only disease status retained as prognostic factor (p<0.01, HR=1.77). For CR1 patients, stem cell source was significant prognostic factor on multivariate analysis (5y-OS = 41.7%, 66.7%, and 79.3% for peripheral blood, cord blood, bone marrow; p = 0.023). When we focused on immunophenotype, stem cell source retained their effect only for patients with T-ALL. For CR2 patients, central nerves system involvement at diagnosis (p=0.02, HR=7.2), S classification (p=0.03, HR=1.2), and NCI risk (p=0.04, HR=2.5) were significant prognostic factors on multivariate analysis. S classification retained its prognostic impact only for patients with BCP-ALL (p=0.01, HR=1.5). For non-CR patients, NCI or JACLS risk classification at first diagnosis, S classification, frequency of relapse before HSCT, stem cell source, and conditioning for HSCT did not affect treatment outcome. Interestingly, non-CR patients with high-hyperdiploid (HHD) (n=5) had a significantly better 5y-OS (80%) than the other subtypes. In multivariate analysis, age at diagnosis (<10 years, p=0.04, HR=2.0)) and HHD (p=0.006, HR=1.74) contribute to the better outcome of HSCT in non-CR. Conclusion: The current study showed that the prognostic factors for HSCT varied according to the disease status or disease immunophenotype. Also, it is noteworthy that HHD patients may be rescued even in non-CR status by HSCT. Disclosures No relevant conflicts of interest to declare.

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4674-4680 ◽  
Author(s):  
Maha El-Zimaity ◽  
Rima Saliba ◽  
Kawah Chan ◽  
Munir Shahjahan ◽  
Antonio Carrasco ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hemorrhagic Cystitis ◽  
Lymphocytic Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Blood And Marrow Transplantation ◽  
Stem Cell Source ◽  
Donor Type ◽  
Total Body ◽  
Unrelated Cord Blood

Abstract Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogenous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15; mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations. (Blood. 2004;103:4674-4680)

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