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.

scholarly journals Clinical Characteristics, Biological Markers and Comorbidity Indexes As Predictors of Transplant-Related Mortality after Allogeneic Hematopoietic Stem Cell Transplantation: Which One Should We Choose?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3478-3478
Author(s):  
Alienor Xhaard ◽  
Renato Cunha ◽  
Marc Busson ◽  
Marie Robin ◽  
Nathalie Dhedin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Telomere Length ◽  
Cell Transplantation ◽  
Research Funding ◽  
Disease Risk ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Recipient Age ◽  
The Impact

Abstract Treatment-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HSCT) is a major concern and remains difficult to predict adequately. Several pre-transplant characteristics of patients and disease are associated with TRM. Comorbidity indexes, including pre-transplant assessment of mortality (PAM) and the hematopoietic cell transplantation comorbidity index (HCT-CI), have been developed in an attempt to predict TRM. Biologic markers, such as ferritin, C-reactive protein (CRP) and, more recently, telomere length, also correlate with TRM. However, the cumulative impact of these factors on TRM has not been addressed. Here, we investigated the impact of pre-transplant clinical factors, comorbidity indexes and biologic markers on TRM in 670 consecutive patients from a single center who received a first allogeneic HSCT between January 2006 and June 2012. Clinical factors considered were: year of transplantation, donor and recipient ages, gender and CMV serological status, disease risk (based on the American Society for Blood and Marrow Transplantation Request for Information 2006 risk scoring schema), stem cell source, and HLA matching. Comorbidities were evaluated by PAM and HCT-CI, and coded prospectively for all patients by a single observer. HCT-CI and PAM scores were ranked into previously published categories (0, 1-2, ≥3 for HCT-CI and 9-16, 17-23, 24-30 and 31-44 for PAM; Sorror, Blood 2005; Parimon, Annals Intern. Med. 2006). Ferritin, CRP and biological data for comorbidity indexes were recorded within 2 weeks prior to HSCT. Recipient telomere lengths were determined in peripheral blood leukocytes by qPCR and adjusted for age by the telomere attrition rate observed in donors.Our analysis categorized the population into quartiles and divided patients into 2 groups: shorter telomeres (first quartile) versus longer telomeres (upper 3 quartiles). The entire patient cohort was subsequently divided into 3 groups by data availability: Group 1 (G1), the entire population (n=670) for whom all clinical data were available; G2, 488 patients with clinical and comorbidity index data (pulmonary function tests were not systematically performed during the early study period); and G3, for whom pre-transplant telomere length was available (n=178). Univariate and multivariate methods developed by Fine and Gray for competing risks studies were used to assess prognostic TRM factors, with relapse as a competing event. Table 1 shows patient characteristics. Significant differences between G1 and G2 were found for mean donor and recipient ages, sex mismatch, HLA matching, stem cell source, disease risk, and year of transplantation. Median follow-up was 36 months, overall survival at 5 years for the entire cohort was 60%, and TRM was 18%. In G1, factors significantly associated with higher TRM in multivariate analysis were: recipient age (HR, 1.02, 95%CI [1.0-1.03], p=0.005), CMV seropositive recipient/seronegative donor (R+/D-) (HR, 1.98, 95%CI [1.34-2.92], p=0.001) and mismatched unrelated donor (MMUD) (HR, 2.28, 95%CI [1.38-3.74], p=0.001). In G2, the same factors [recipient age (HR, 1.01, 95%CI [1.00-1.03], p=0.027), CMV R+/D- (HR, 1.91, 95%CI [1.22-2.99], p=0.005), MMUD (HR, 2.55, 95%CI [1.48-4.42], p=0.001)] were associated with higher rates of TRM, whereas PAM showed a trend for higher TRM (HR, 1.41, 95%CI [0.99-1.99], p=0.05). HCT-CI, ferritin, and CRP were not associated with TRM. In G3, only MMUD (HR, 2.82, 95%CI [1.06-7.46], p=0.037) was associated with higher TRM. However, in analysis restricted to patients transplanted from an HLA-matched related or unrelated donor, recipient age (HR, 1.03, 95%CI [1.00-1.06], p=0.027) and telomere length (HR, 2.45, 95%CI [1.07-5.59], p=0.033) were independently associated with higher TRM. This is the first study to investigate the impact of clinical and biological pre-transplant factors and comorbidity indexes on TRM after allogeneic HSCT in a large cohort of patients. Best results were obtained with young patients transplanted from an HLA-matched donor, with CMV other than R+/D-. High comorbidity scores (evaluated by PAM) were marginally associated with higher TRM. In G3 (pre-transplant telomere length available), only HLA-mismatch was significantly associated with higher TRM. Disclosures Peffault De Latour: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Alexion: Consultancy, Honoraria, Research Funding.

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.

Outcome of Patients Developing GVHD after DLI for CML Relapse from HLA-Identical Sibling or VUD HSCT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1817-1817
Author(s):  
Yves Chalandon ◽  
Christoph Schmid ◽  
Kimmo Porkka ◽  
Alvaro Urbano-Ispizua ◽  
Bernd Hertenstein ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Chronic Gvhd ◽  
Median Number ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Initial Cell ◽  
Cell Dose ◽  
Stem Cell Source ◽  
Related Mortality

Abstract Using data submitted to the EBMT registry, we analyzed outcome on 344 patients (pts) who had received donor lymphocyte infusions (DLI) for relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) in 31 centers. 113/344 pts (33%) developed acute graft-versus-host disease (aGVHD) a median of 50 days post DLI (max grade: I=42, II=30, III=31, IV=6)(60% grade II–IV). Organs involved (%): skin (88), liver (42), gut (30). Median age was 38 (4–59), 58% pts were male, 62 transplants were HLA-identical sibling and 51 unrelated. 74 were T-cell depleted, 92 transplanted in CP1, 21 beyond CP1. Relapse was molecular in 19 pts, cytogenetic in 31, hematological in 49, accelerated or blastic in 12. Median initial cell dose was 107CD3+ cells/kg (0.01–32), median number of DLI was 1 (1–10). aGvHD was treated with prednisone in 92% of pts, CSA in 52 %, ATG and monoclonal antibodies in 2% and other in 19%. aGVHD resolved in 53% of the pts within a median of 63 d (7–546). 82/344 pts (24%) had chronic GVHD (cGVHD)(30 limited, 50 extensive, 2 not specified), of those 46 (56%) following aGVHD post DLI. Organs involved (%): skin (75), liver (35), lungs (13), mouth (43), eyes (22) and gut (5). Median age was 35 (6–58), 51% were male, stem cell source was PB in 15% and marrow in 85%, 43 underwent HLA-identical sibling HSCT and 39 unrelated donor HSCT. Forty-three were T-cell depleted, 66 transplanted in CP1, 16 beyond CP1. Relapse was molecular in 21 pts, cytogenetic in 29, hematological in 22, accelerated or blastic in 7. Median initial cell dose was 107 CD3+ cells/kg (0.05–40), median number of DLI was 1 (1–7). 61 pts are alive with a median follow-up of 50 mth. Treatment was with steroids in 83% of pts, CSA in 58 %, MMF in 20%, thalidomide in 15%, photopheresis in 15%, PUVA in 10% and other in 17%. cGVHD resolved in 39% of the pts within a median of 354 d (44–1588). The estimated 5-y OS post-DLI was significantly lower in pts who developed aGVHD post-DLI, 61 ± 10% vs 74 ± 7% in the one that did not, p=0.007 and also a tendency to have a lower 5-y EFS, 58 ± 10% vs 65 ± 7%, p=0.19. Median duration of response to DLI in aGVHD pts was 4 y. aGVHD post-DLI did not influence the relapse rate (5 ± 5% vs 6 ± 5% in the absence of aGVHD). 5-y DLI related mortality was significantly higher in aGVHD pts, 31 ± 8% vs 4 ± 4%, p<0.00001. On the other hand, pts that developed cGVHD post-DLI had a tendency to have a better 5-y OS and EFS, 74 ± 11% and 71 ± 11% respectively vs 69 ± 6% and 62 ± 7% in those that did not, p=0.32 and 0.09. This was related to a tendency to lower incidence of relapse, 2 ± 3% in pts with cGVHD vs 9 ± 6% without, p=0.2. DLI related mortality was not different, 11 ± 8% vs 10 ± 5%, p=0.77. aGVHD post-DLI for CML relapse is mainly of advanced stage and negatively influence OS and EFS with a higher DLI related mortality. cGVHD post-DLI is mainly extensive, but pts with cGHVD tend to have better outcome with better 5-y OS, EFS and less relapse than those without, although this was not statistically significant.

Fewer Relapses Following Unrelated Donor Cord Blood (UDCB) Compared to Related or Unrelated Bone Marrow (BM) or Peripheral Blood Cell (PBSC) Transplant in the Treatment of Childhood Relapsed and Very High Risk Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3153-3153
Author(s):  
Donna A. Wall ◽  
Ka Wah Chan ◽  
Bess Bowen ◽  
Lorraine Alexander ◽  
Michael Grimley
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cord Blood ◽  
Hematopoietic Progenitor Cell ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
High Risk Disease ◽  
Cell Source ◽  
Preparative Regimen ◽  
First Remission

Abstract With aggressive primary therapy for ALL children who relapse are presenting to transplant after having received more intensive frontline and salvage therapy - resulting in transplant candidates with more resistant disease and at a higher risk for transplant related morbidity/mortality (TRM). Thus the the current generation of children presenting for allogeneic transplant are much more difficult to treat. With the addition of unrelated donor cord blood as an alternative hematopoietic progenitor cell source there is now an unrelated donor product available for a majority of children in a timely fashion. For the last 5 years we have treated all children with ALL coming to transplant with a standard preparative regimen which has minimally changed over that time period. Over the past year all children have received identical immunosuppression regardless of stem cell source. This allows us to analyze the impact of allogeneic stem cell source on the outcome of transplant - the graft-vs.-leukemia effect of the various HSCT sources. Between 3/2001 and 7/2006 a total of 54 transplants (txp) were performed at Texas Transplant Institute for treatment of childhood ALL (median age 8 yr, range 0–17 yrs). There were 13 txp for standard risk disease (CR1: Ph+, requiring more than 28 d to achieve CR1, severe hypodiploidy; CR2 with first remission >36 mo) − 7 CB and 6 BM/PBSC. There were 41 txp for high risk disease (CR2 with first remission <36 mo, >CR2 or not in remission at time of txp) − 31 CB and 10 BM/PBSC. All received TBI (1200 cGy in 6 fractions), cyclophosphamide 120 mg/kg, and either thio-tepa 10mg/kg or VP16 1500 mg/m2, or an additional 150 cGy TBI. There was no adjustment in the preparative regimen for the donor source. The first 26 CB transplants (UDCBT) received ATG 30 mg/kg x 3 days prior to txp, the subsequent patients did not receive ATG. There were 38 UDCBT, 14 matched sibling donor and one each of unrelated donor and partial matched family member (6 PBSC, 8 BM). GVHD prophylaxis was a calcineurin inhibitor combined with steroid or mini-methotrexate and/or sirolimus. The time to ANC>500 and platelet recovery was prolonged in the UDCBT group compared to BM/PBSC (19 vs. 14.5 d for ANC, 57 vs. 23 d for platelet >20,000). There were two graft failures in the UDCBT group - both CR1 patients and both salvaged with a second UDCBT. With median f/u of 270 and 350 days for CB and BM/PBSC respectively there was a significant difference in the risk for relapse (5/37 vs. 9/16; p<0.03), TRM (8/37 – 1 GVHD, 3 MOSF, 2 bacterial, 1 leukoencephalopathy, 1 pulmonary vs. 2/16 -fungus, LPD; p= 0.7). KM survival analysis is shown below: Relapses/N 1 yr DFS 2 yr DFS Standard UDCBT 0/7 86% 86% Standard BM/PBSC 3/6 60% 30% HR UDCBT 5/31 62% 56% HR BM/PBSC 6/10 60% 50% Importantly there have continued to be late deaths in the BM/PBSC group due to relapse with the CB curves remaining stable after 18 months post txp. Despite 80% of the CBT being performed for children with high risk disease there were fewer relapses in the UDCBT cohort suggesting a robust allogeneic effect against ALL in the setting of UDCBT.

scholarly journals What Is the Most Appropriate Source for Hematopoietic Stem Cell Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Itır Sirinoglu Demiriz ◽  
Emre Tekgunduz ◽  
Fevzi Altuntas
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Cell Source ◽  
Selection Of

The introduction of peripheral stem cell (PSC) and cord blood (CB) as an alternative to bone marrow (BM) recently has caused important changes on hematopoietic stem cell transplantation (HSCT) practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

A Comparison of Stem Cell Source in Recipients of T-Cell Depleted Myeloablative Transplants for Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 46-46
Author(s):  
B.E. Shaw ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
J. Apperley ◽  
G. Cook ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Increased Risk ◽  
Significant Difference ◽  
Cell Source ◽  
The Impact

Abstract The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in transplant related mortality (TRM) and decrease in survival (OS) in T-cell replete transplants. We sought to analyse the impact of PBSC compared to BM in a cohort of UD transplant recipients, where T-cell depleting agents (in-vivo campath in >90%) were included in the transplant conditioning. The study included 145 patients transplanted between January 2000 and March 2006: CML- 35 in 1CP; acute leukaemia (AML in 61, ALL in 49)-110 in CR1 or 2. All had myeloablative conditioning regimens and received grafts with 9–10/10 matched HLA alleles. 86 patients received BM and 59 PBSC. There were no associations between the stem cell source and any transplant variable (including disease and stage). There was a trend to an increased use of PBSC in patients with a single antigen mismatch (p=0.052). All evaluable patients achieved neutrophil engraftment, with a significantly faster time to engraft in recipients of PBSC compared to BM (16 vs 20 days; p=0.0003). The incidence of acute GvHD was 46% (grade I in 50%, II in 41%, III in 8%, IV in 2%). This was significantly higher in recipients of PBSC (60%) compared to BM (36%; p=0.006), however there was no increase in either II/IV (p=0.69) or III/IV (p=0.18) disease in PBSC recipients. In univariate analysis, the presence of a single HLA mismatch (p=0.026) was the only other variable to be associated with an increase in acute GvHD. In a logistic regression model including both these variables, the use of PBSC remained significantly associated with an increase in aGvHD (OR=2.3; 95% CI 1.1,4.7;p=0.020). The TRM was 14%, 27% and 39% at 100 days, 1 and 5 years respectively. At none of these time points was the stem cell source associated with a significant difference in TRM. The 5-year incidence of chronic GvHD was 58% (BM 55%, PBSC 60%; NS), extensive disease in one third, and of relapse was 61% (BM 60%, PBSC 62%; NS). The 5-years OS was 41% with a median follow-up of 3.4 years (0.5–7.1). This was 44% using PBSC and 40% using BM (NS). In conclusion, although we observed an increase in acute GVHD with PBSC this was only of grade 1 disease. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM, in recipients of T-cell depleted myeloablative transplants for leukaemia.

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.

Is Initial CD3+ T Cell Dose in Donor Lymphocyte Infusion for Relapsed Hematological Malignancies a Prognostic Determinant?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5483-5483
Author(s):  
Erden Atilla ◽  
Pinar Ataca ◽  
Selami Kocak Toprak ◽  
Meltem Kurt Yuksel ◽  
Pervin Topcuoglu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
T Cell ◽  
Hematological Malignancies ◽  
Donor Lymphocyte Infusion ◽  
Time Interval ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
Stem Cell Source ◽  
Cell Source

Abstract Introduction: Patients after relapsing allogeneic hematopoietic stem cell transplantation (AHSCT) have a treatment option of donor lymphocyte infusion (DLI). DLI is a form of adoptive immunotherapy which induces graft versus leukemia effect. Severe forms of graft versus host disease (GVHD) and marrow aplasia are known complications. In this study, we aimed to detect the effect of the infused CD3+ T cell dose on response, GVHD and overall survival (OS) of hematological malignancies after AHSCT. Methods: We retrospectively evaluated 78 DLI procedures in 57 patients with different hematological malignancies for relapse after AHSCT from June 2000 through June 2015. Initial DLI CD3+ cell dose/kg recipient body weight was ≤ 1x10^7 (n=20; Group 1), >1.0 to ≤ 5 x10^7 (n=29; Group 2), 5-10 x10^7 (n=29; Group 3). Chi-square test was used in comparison between groups. P<.05 was considered statistically significant. Results: The median age during DLI was 33,8 ± 13,2 (range 16-67 years) in 57 patients (38M/19F). The median time interval from HCT to DLI was 8.08 (2-69) months. Ten patients (18%) had bone marrow while 47 patients (82%) had peripheral blood as stem cell source. All patients received transplants from HLA-matched related siblings. There was no difference found between the three groups according to age, diagnosis, stem cell source and conditioning regimen. Achieving complete remission after DLI was detected in thirty two (56%) patients. Disease status after DLI, acute and chronic GVHD rates were not statistically different between the groups. Overall survival which was not statistically significant according to initial DLI cell dose at 2 years were 25%, 38% and 24%, respectively. Conclusion: An initial DLI CD3+ cell dose of 10 x10e7 or higher has been shown improve overall survival but increase GVHD rates with no effect on risk of relapse in previous reports. Response rate, GVHD and survival outcomes were found to be similar in comparison of three different DLI dose groups in our study. Disclosures No relevant conflicts of interest to declare.

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