Donor Lymphocyte Infusions (DLI) After Peripheral Blood Stem Cell Transplantation. A Retrospective Analysis of 357 Patients by the Chronic Leukemias Working Party EBMT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3309-3309
Author(s):  
Grzegorz Wladyslaw Basak ◽  
Anja van Biezen ◽  
Ronald Brand ◽  
Christoph Schmid ◽  
Cesare Guglielmi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Molecular Cytogenetic ◽  
Stem Cell Source ◽  
Cell Source ◽  
Grade Ii

Abstract Abstract 3309 Poster Board III-197 Donor Lymphocyte Infusions (DLI) constitute a potent therapeutic option for treating relapse of chronic myelogenous leukemia (CML) after hematopoietic stem cell transplantation (SCT) inducing durable remissions in the majority of patients. A number of factors is known to influence the efficiency of DLI. A preliminary analysis of EBMT data had suggested that DLI efficiency might be inferior after peripheral blood stem cell transplantation (PBSCT) as compared to DLI following bone marrow transplantation (BMT) (Schmid et al. ASH, 2005). To control for a number of other factors that were not known at the time of the previous analysis, we repeated this analysis based on the results of 357 patients treated with DLI following PBSCT (N=108) and BMT (N=249). We limited the analysis to patients who relapsed after standard intensity conditioning SCT from HLA-identical family donors in first chronic phase of disease. The median age of patients was 39 years (range 18-60) with predominance of males (59%). 53% of patients with known data were CMV positive and in 44% of the patients there was a sex-mismatch with the stem cell donor. SCTs have been performed between 1994 and 2007 (median year: 1998) and the conditioning treatment included total body irradiation (TBI) in 68% and T cell depletion in 44% of patients. 92% of patients with known data achieved complete remission after SCT while grade II-IV acute GvHD occurred in 18% of patients and extensive chronic GvHD in 17% of patients. Median time to relapse was 17 months (range 0.6-129) and median time from SCT to first DLI infusion was 23 months (range 0.6-142). Looking at the patients with known data at the time of first DLI infusion, the relapse could be classified as molecular/cytogenetic in 63%, hematologic in 27% and transformed in 10% of patients. The median year of first DLI was 2000 ranging from 1995 to 2007. As the initial DLI infusion, 9% of patients received <1×10e6, 62% 1.1-10×10e6 and 29% received >10×10e6 CD3+ cells/kg. However, the comparative analysis of groups based on the stem cell source revealed that the group of patients transplanted with PBSCs included significantly more males (68 vs. 56%), were older (median age 42 vs. 39) and underwent more frequently T cell depletion at SCT (72 vs. 34%,). PBSCTs have been performed more recently (median year 1999 vs. 1997) and both duration of remission and time from SCT to first DLI were shorter after PBSCT (median duration: 12 vs. 21 months and 14 vs. 26 months respectively). The initial cell dose in patients from PBSCT arm was significantly lower than in BMT group (≤10×10e6 CD3+/kg in 89% vs. 65% of patients). Similarly to the previous study, we also observed a trend towards superior overall survival after DLI in BMT group compared to PBSCT group, especially in the early post-transplant period. The actuarial probability of survival at five years from DLI was 77% in PBSCT group and 79% in BMT group. However the differences were not statistically significant (p=0.77). The source of stem cells did not influence the occurrence of molecular/cytogenetic remissions after DLI (80% vs. 77%) grade II-IV acute GVHD (16% vs. 16%), chronic GVHD (23% vs. 30%) and myelosuppression (10% vs. 16%). In order to search for factors having impact on survival of analyzed patients, we performed both univariate and multivariate survival analyses. The univariate analysis revealed that interval from SCT to DLI longer than 2 years (p=0.001), date of DLI after 2000 (p=0.026) and molecular/cytogenetic stage of relapse at DLI (p<0.001) were associated with favorable survival. Similarly, the multivariate Cox analysis identified interval between SCT and DLI (HR= 0.50, CI: 0.3-0.8; p=0.01 for after 2 years), date of DLI (HR=0.63, CI:0.4-1.0; p=0.07 for after 1999), and stage of relapse (HR=2.8, CI:1.2-6.5; p=0.02 for HemCR and HR=3.6, CI:1.8-7.0; p<0.001 for missing data group), but not for stem cell source (HR=0.95, CI 0.56-1.6 ;p=0.86) as independent factors affecting survival. Based on our retrospective data from EBMT registry covering a period of 14 years of SCT and DLI, it seems that the PBSCT does not affect the efficiency of DLI compared to BMT. Therefore, keeping all limitations of a retrospective analysis in mind, it seems that differences in efficacy of DLI do not influence the decision whether PBSC or BM should be used as stem cell source for allogeneic SCT in CML in first chronic phase. Disclosures No relevant conflicts of interest to declare.

Transplantation of Peripheral Blood Stem Cells from Unrelated Donors Is Not Associated with Inferior Survival Compared to Bone Marrow Transplantation in Children with Hematologic Malignancies - A Registry Analysis from the German/Austrian Pediatric Registry for Stem Cell Transplantation (PRST).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3109-3109
Author(s):  
Roland Meisel ◽  
Caroline Spohr ◽  
Thomas Klingebiel ◽  
Dagmar Dilloo
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Stem Cell Source ◽  
Cell Source ◽  
Unrelated Donors

Abstract The optimum stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT) remains highly controversial. A recent study in older children and adolescents receiving HSCT from HLA-identical sibling donors has revealed higher mortality after peripheral blood stem cell (PBSC) compared to bone marrow (BM) transplantation (Eapen et al, JCO, 2004). However, despite the increasing use of PBSC in pediatric HSCT from matched unrelated donors (MUD), comparative studies on the relative risks and benefits of both stem cell sources are lacking. We therefore analysed the outcome of unrelated PBSC (n=118) and BM (n=102) transplants reported to the German/Austrian Pediatric Registry for Stem Cell Transplantation (PRST) between 1998 and 2003. Patients with hematologic malignancies (ALL, AML, CML, or MDS), who had received unmanipulated HSCT from ≥ 5/6 HLA antigen-matched unrelated donors following myeloablative conditioning were included into the analysis. PBSC and BM groups were comparable with regard to sex, age, CMV serostatus, GvHD prophylaxis, disease status at transplant, prophylactic growth factor use and degree of HLA-matching, while differences were detected in disease category (more MDS patients in PBSC group, p=0.02), transplanted cell dose (higher CD34-cell graft content in PBSC group, p=0.001) and median year of transplant (PBSC transplantations were more recent, p=0.01). Engraftment was achieved significantly faster after PBSC compared to BM transplantation: 15 vs. 19 days for neutrophil engraftment (p=0.001) and 21 vs. 25 days for platelet engraftment (p<0.01). The rate of acute GvHD grade II–IV (PBSC vs. BM: 44% vs. 39%, p=0.48) and severe acute GvHD Grade III/IV (29% vs. 21%, p=0.17) did not significantly differ between both groups. Moreover, the incidence of chronic GvHD (PBSC vs BM: 35% vs 33%, p=0.9) and extensive chronic GvHD (18% vs 18%, p=0.85) was identical at 3 years post transplant. In the PBSC group there was a statistically non-significant trend towards a higher risk for treatment-related mortality (PBSC vs BM: 34% vs 25%, p=0.14) and a lower risk for death of disease (PBSC vs. BM: 14% vs. 23%, p=0.16). However, this did no translate into a survival difference. With a median follow up of 2.9 years (PBSC) and 3.1 years (BM) overall survival (PBSC vs. BM: 50±5% vs. 46±6%; p=0.63) and event-free survival (45±5% vs. 44±6%; p=0.59) is comparable between both groups. This clinically most relevant result was confirmed in a multivariate analysis showing that advanced disease status at transplant (RR 2.4, 95%-CI 1.5–3.8, p=0.001) is a significant, independent risk factor for treatment failure, while the stem cell source (PBSC vs BM) has no effect (RR 1.1, 95%-CI 0.7–1.6, p=0.8). In summary, our data provide first evidence from a large, registry based analysis, that in pediatric recipients of MUD transplantation the use of PBSC instead of BM is not associated with inferior survival. Therefore, PBSC is a valid alternate stem cell source for pediatric HSCT from MUDs.

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.

Non-Myeloablative Allogeneic Stem Cell Transplantation in 154 Patients (pts) with Chronic Myeloid Leukaemia (CML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4975-4975
Author(s):  
Malek Benakli ◽  
Rose-Marie Hamladji ◽  
Redhouane Ahmed Nacer ◽  
Amina Talbi ◽  
Farih Mehdid ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Transfusion Requirements

Abstract Background: Allogeneic stem cell transplantation using a reduced intensity or nonmyeloablative conditioning (NSCT) represents an attractive treatment modality in CML. The rationale behind such approach is to decrease toxicity while inducing the graft-versus-leukemia (GVL) effect. Because of its significantly lower cost in comparison to Imatinib mesylate, NSCT may be considered an early treatment option in countries where limited resources. Material and Methods: Between April 2001 and December 2006, we treated 154 CML patients (131 in first chronic phase, 23 in accelerated phase) with NSCT from an HLA-identical family donor. The majority of pts has a Gratwohl score <2 prior to NSCT (n=115; 74,6%). The conditioning regimen included Fludarabine 150 mg/m2 and oral Busulfan 8 mg /kg (139 pts). GVHD prophylaxis consisted of association ciclosporine (CSA)-Mycophenolate (MMF). 15 pts received an additional prophylaxis with antithymocyte globulin (ATG). Median age was 35 (range, 18–55) years, and the sex-ratio (M/F) 0,87. The median time from diagnosis to NSCT was 11 (range, 4–50) months. All pts received G-CSF mobilised peripheral blood stem cells, median CD34+ cells count: 7,02.106/kg (range, 1,28–44,9). Results: Leucopenia is found almost at 71 pts (46,1%). The median time to achieve ANC >500. 109/l granulocytes was 14 (range, 7–24) days, and median time of aplasia was 7 (range, 2–19) days. Transfusion requirements were significantly reduced, only 3 pts (1,9%) required red blood cells transfusions. Only 15 pts (9,7%) needed platelets transfusions. Acute GVHD was seen in 65 cases (43,6%) including 26 (17,4%) cases of grade III–IV and 32 cases (21%) of late onset acute GVHD occurring after day 100 post-NSCT. 93 pts (67,3%) had chronic GVHD, of whom 58 with an extensive form. 23 pts (15,4%) had CMV reactivation. 24 pts (16,1%) relapsed (15 in chronic phase, 7 in blast crisis and 2 with a molecular relapse), but 11 pts could be salvaged and are currently in remission (7 after immunosupression discontinuation, one after DLI and 3 after a second conventional allograft). The chimerism of donor origin (STR-PCR method) of patients in remission was at an average of 74% at day 30, 80% at d100, 93% at 6 months, 97% at 1 year, and 99% at 2 years. Fifty pts (33,5%) have died, of whom 39 (22,1%) from GVHD and 10 (6,7%) from disease relapse. Transplant Related Mortality (TRM) at 100 days was 6%, but rose to 31,5% at 3 years. At last follow-up (median, 32 (range 6–68) months), 99 pts (66,4%) are still alive, 97 (65,1%) pts in hematologic remission; of whom 76 (78,3%) in complete molecular remission evaluated by RT-PCR. Overall survival and progression-free survival at 5 years are 61% and 51,6% respectively. Conclusion. The study demonstrates a relatively low rate of short-term toxicities after NSCT. However, long-term TRM is still high because of the GVHD. The GVL effect is well admited. The relapse can be often controled by immunomodulation (stoppage of immunosuppression, DLI) and eventually by second myeloablative allograft.

Allogeneic Stem Cell Transplantation for Acquired Aplastic Anemia: Better Outcome with Bone Marrow as Compared to Peripheral Blood in HLA-Matched Sibling Donor Transplantation and Improved Outcome Over Time After Matched Unrelated Donor Transplantation. A Retrospective Analysis of Transplants Reported to the German Registry for Stem Cell Transplantation (DRST).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 876-876
Author(s):  
Hubert Schrezenmeier ◽  
Ulrike Feldmann ◽  
Hellmut Ottinger ◽  
Matthias Eder ◽  
Monika Führer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Probability Of Survival ◽  
Stem Cell Source ◽  
Cell Source ◽  
Matched Sibling ◽  
German Registry

Abstract Abstract 876 Background: Transplantation of bone marrow (BM) from a HLA-matched sibling donor is an effective treatment for severe aplastic anemia (AA) with long-term survival in excess of 80%. In the recent years there were two trends in allogeneic stem cell transplantation (SCT) for AA: (1) increasing proportion of transplants performed from matched unrelated donors (MUD) and (2) increasing proportion of transplants using peripheral blood progenitor cells (PBSC) as stem cell source instead of BM. A similar switch to PBSC over BM grafts is reported in leukemia transplants. PBSC grafts for leukemia are associated with higher rates of chronic graft-versus-host disease (cGVHD). This adverse consequence may be offset by lower rates of leukemia relapse in some settings. In contrast, there is no perceived benefit of cGVHD for AA. A recent retrospective analysis of EBMT/CIBMTR reported worse outcome after PBSCT compared to BMT in young patients after HLA-matched sibling (sib) transplantation. The impact of stem cell source on outcome after MUD transplants has not been studied in detail so far. Some reports on favourable results after MUD SCT prompted the discussion whether MUD SCT should be performed earlier in the treatment algorithm in AA instead of considering it as salvage treatment after failure of immunosuppressive treatment. Therefore we performed a retrospective study on the dataset of the German Registry of Stem Cell Transplantations (DRST) to (1) analyze outcome after MUD compared to sib SCT and (2) to study impact of stem cell source (PBSC vs BM) on both sibling and MUD SCT and (3) to analyze impact of transplant period (1998-2002 vs. 2003-2008). Results: We analyzed 182 sib SCT and 114 MUD SCT (first transplants only). The interval between diagnosis and transplant was significantly longer for MUD SCT as compared to sib SCT (median 98.5 days vs. 511.5 days; p<0.001 ) suggesting that the majority of sib SCT were performed upfront whereas MUD SCT in the majority of cases was performed after failure of other treatments. Median age was 28.5 years (sib SCT) and 30 years (MUD) years (p=0.41). PBSC were used as stem cell source in 50.5% of sib SCT and 61.4% of MUD (p=0.097). 5-year probability of survival was 84.6% (95%-CI: 79.3-90.3%) after sib SCT and 70.1% (95%-CI. 61.8-79.6%) after MUD (p<0.003). In univariate comparison age at transplant has significant impact on survival: After sib SCT 5-year probability of survival in patients ≤ 30 years vs. > 30 years was 94.5% (95%-CI: 90.0-99.3%) vs. 73.5% (95%-CI: 64.3-84.1%)(p<0.001) . 5-year probability of survival after MUD SCT in patients ≤ 30 years vs. > 30 years was 77.7% (95%-CI: 67.3-89.7%) and 60.6 (95%-CI: 48.2-76.2%) (p=0.044). In the most recent period (2003-2008) 2-year probability of survival was 81.6% (95%-CI: 72.9-91.3%) after sib SCT (n=80) and 75.6 (66.1 – 86.5%) after MUD SCT (n=73) (p=0.34). After sib SCT survival was significantly better with BM as compared to PBSCT (5-yr. prob. 95.3%; 95%-CI: 90.9-99.9%; n=89 vs. 74.1%, 95%-CI: 65.1-84.2%; n=92; p<0.001) and cumulative incidence of chronic GvHD was significantly higher with PBSCT as compared to BM (47.0% vs. 18.4%; p<0.01). Cumulative incidence of acute GvHD II-IV did not differ significantly between BM and PBSC. In contrast, stem cells source did neither significantly affect overall survival nor cumulative incidence of acute or chronic GvHD after MUD. In multivariate analysis of the sib SCT older age (>30 years) and use of PBSC were significant risk factors for mortality (Hazard Ratio (HR) 3.4 (1.2-9.3) and HR 4.0 (1.3-12.2). Other variables in the model (conditioning regimen; GvHD prophylaxis; sex match; time diagnosis to transplant and transplant period) were not significant. For MUD SCT none of these variables were significant in a multivariate model. Conclusion: These results indicate that BM grafts should be preferred to PBSC in patients undergoing HLA-identical sib SCT for AA. In contrast, no negative impact of stem cell source on outcome after MUD SCT could be demonstrated. Results of MUD SCT substantially improved over time. In the most recent period from 2003- 2008 the probability of survival after MUD and HLA-identical sib SCT was no longer different. So far majority of MUD transplants were performed late after diagnosis, mostly after failure of immunosuppression. Re-assessment of both the indication of MUD SCT for AA and the timing of MUD SCT is warranted. Supported by the Deutsche José Carreras Leukämie-Stiftung. Disclosures: No relevant conflicts of interest to declare.

Donor Lymphocyte Transfusion (DLT) in the Treatment of Relapsed CML after Allogeneic PBSCT - A Retrospective Analysis of 346 Patients by the EBMT Chronic Leukemia Working Party.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 704-704
Author(s):  
Christoph Schmid ◽  
Anja v. Biezen ◽  
Kimmo Porkka ◽  
Yves Chalandon ◽  
Alvaro Urbano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Working Party ◽  
Disease Stage ◽  
Published Data ◽  
Molecular Cytogenetic ◽  
Allogeneic Pbsct

Abstract DLT has become the gold standard for the treatment of reccurrent CML after allogeneic stem cell transplantation. However, so far, published data are based on DLT following bone marrow transplantation (BMT). During recent years, mobilized peripheral blood stem cell transplantation (PBSCT) have been increasingly performed. To evaluate the efficacy of DLT following PBSCT, we retrospectively analysed the results of 86 patients treated with DLT for CML relapse after PBSCT from HLA-identical family donors. Results were compared to 260 patients receiving DLT for relapse after related BMT. Reduced intensity transplants were excluded. BMT and PBSCT groups were balanced in terms of patient age (median: 40 vs 42 y), conditioning, stage at transplant (84% vs 76% in first chronic phase (CP) p=.2), and stage at relapse (molecular/cytogenetic: 59% both, CP: 28% vs 20%, advanced: 13% vs 21%, p=.2). However, BMT patients had been transplanted in earlier years (median: 1994 vs.1998, p&lt;.001), had a longer remission after transplantation (median: 677 vs. 275 d, p&lt;.001), and had experienced more aGvHD after transplantation (58% vs. 34%, p&lt;.001). Complete molecular or cytogentic remission was achieved in 71% of the patients, with a trend towards better response in BMT recipients (p=.06). Overall (OS) and event free survival (EFS) at five years from DLT are shown in table 1. Outcome was significantly superior in BMT recipients, in particular if DLT was given for hematological, rather than cytogenetic or molecular relapse. In a cox regression model, four factors were associated with better OS/EFS: Transplantation in CP1 (p&lt;.001/.002), early stage at relapse (molecular/cytogenetic vs. hematological, p&lt;.00/&lt;.001), a longer remission after transplantation (p=.005/.028), and BM vs. PBSC for transplantation (p= .003/.004). In contrast, age of patient and donor, acute or chronic GvHD after transplantation, the use of chemotherapy or imatinib before DLT, and the initial number of transfused CD3+ cells were not significant. The results of this retrospective study suggest a reduced efficacy of DLT in CML relapse following related allogeneic PBSCT as compared to BMT. This effect seems to be independent from established risk factors as disease stage and remission duration. However, since several adverse factors are not equally distributed among the two groups, a bias might be induced, although no statistically significant imbalance could be detected. Therefore, the observation needs to be confirmed in a larger cohort or a prospective study. Table 1. Outcome after DLT No BMT PBSCT p Total 346 260 86 OS at five years from DLT 71% 75% 66% &lt; .001 EFS at five years from DLT 61% 64% 41% &lt; . 001

Analysis of a New graft–versus-host Disease (GvHD) Prophylaxis Regimen with Additional Enteric-coated Mycophenolate Sodium (EC-MPS) Starting 10 Days after Unrelated Allogeneic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2202-2202
Author(s):  
Herbert G. Sayer ◽  
Lars-Olof Mügge ◽  
Sebastian Scholl ◽  
Anne Klink ◽  
Kristina Schilling ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Grade Iii

Abstract Introduction: Acute GvHD has, despite established immunosuppressive prophylaxis regimens, significant impact on acute morbidity and mortality following allogeneic stem cell transplantation (SCT). In the unrelated or even non-matched unrelated situation new GvHD-prophylaxis regimens balancing GvHD and graft-versus-leukaemia effect are needed. EC-MPS and mycophenolate mofetil [MMF] are effective immunosuppressants by inhibition of T- and B-cell proliferation. Primary study aims in this ethical board approved, prospective, single-centre, open phase II trial were (1) feasibility of prolongatedly started oral EC-MPS and (2) reduction in the rate of GvHD in unrelated allogeneic SCT. Patients and Methods: EC-MPS [Myfortic ®] 720 mg twice a day orally starting at day +10 after SCT in addition to standard GvHD prophylaxis, consisting of cyclosporine (CSA) 3 mg/kg continuous intravenous infusion with or without methotrexate (MTX) 15 mg/m2 day +1 and 10 mg/m2 day +3,+6,+11 intravenous push, was evaluated. According to the protocol, EC-MPS was tapered from day +40, if no acute GvHD-signs were present. 54 patients, including 8 patients from a previous pilot trial, with advanced haematological malignancies (n=28) or in first remission of acute leukaemia (n=26) between 8/03 and 12/07 were evaluated. The patients had either a 10/10 HLA-matched (n=32) or a 8-9/10 HLA mismatched unrelated donor (n=22). 32 (59%) patients received 40 mg/kg antithymocyte globulin (ATG), with 8 Gray total body irradiation (TBI) and cyclophosphamide (CY), or with fludarabine 120mg/m2, busulfan 8mg/kg or treosulfan 8–12 mg/kg. 12 or 8 Gray TBI and 120 mg/kg CY followed by MTX i.v. were administered to 22 (41%) patients. Results: A median of 5.7 (range: 0.9–9.9) unmanipulated G-CSF-mobilized CD-34 positive stem cells per kg were given on day 0. All of the 23 women and 31 men (median age 48 years (range: 20–65)), except one patient, showed a leukocyte engraftment on median day +14 (range: 9–35). Platelet engraftment was observed on median day +17 (range: 9–132). In 12 patients (22%) initially i.v. MMF (1g twice a day) instead of oral study medication was given temporarily, mostly due to severe mucositis. In six patients (11%) EC-MPS (on day +14, 17, 22, 32, 37, 76) had to be discontinued, due to severe nausea (n=2), neurological toxicity (n=2), graft failure (n=1) and protocol violation (n=1). Acute GvHD grade II-IV was observed in 27 (52%) patients, including 8 (15%) with grade III and 4 (7.5%) with grade IV. The incidence of chronic GvHD was 63 % (n=29) [limited chronic GvHD: 54 % (n=15), extended chronic GvHD: 14% (n=4)] of the 46 patients surviving &gt;100 days after SCT. With 10/10 HLA-matched donors GvHD grade II-IV was seen in 44% (n= 14) [grade III and IV n=5 (16%)], whereas with non fully-matched donors the incidence was 59 % (n=13) [grade III and IV n=7 (32%)]. Chronic GvHD incidence was 50% (14/28) in the fully matched donor situation in contrast to 83% (15/18) in the non-fully matched situation. The conditioning regimen with ATG resulted in a GvHD grade II-IV incidence of 39% (n=12) [GvHD grade III/IV: 19% (n=6)], compared to 68% (n=15) [GvHD grade III/IV: 27% (n=6)] without ATG. With a median follow-up of 16 months (range: 1–56) 28 patients (52%) are alive, 18 fully HLA-matched stem cell recipients (56%) and 10 mismatched HLA recipients (45%). Survival with or without ATG was 50% (n=16) and 55% (n=12), respectively. Twenty-six (48%) patients have died; 12 (22%) due to relapse, 10 (19%) due to acute/chronic GvHD, and 4 (7%) due to infection/secondary cancer without GvHD. Conclusions: EC-MPS with a 10 day prolongated start after transplantation combined with initial standard GvHD prophylaxis in the unrelated stem cell transplantation setting seems to be feasible. Mucositis was the main course for oral intake problems. The toxicity drop-out rate of 7 % should be considered. The analysis of all evaluable patients in the pilot and the prospective trial yielded effectiveness in reducing severe GvHD Grade III/IV, especially in combination with ATG. The MPS application regimen failed to show less incidence of chronic GvHD in the non-fully matched unrelated donor setting. GvHD prevention trials in the future should incorporate new drugs with a different pathway of T-cell inhibition or tolerance induction, respectively.

Multicenter, Prospective Study of Tacrolimus Plus Methotrexate As Graft-Versus-Host Disease Prophylaxis in HLA-Matched Sibling Peripheral Blood Stem Cell Transplantation: Comparison with Cyclosporine Group As Control

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4177-4177
Author(s):  
SeungHwan Shin ◽  
JaeHo Yoon ◽  
SeungAh Yahng ◽  
SungEun Lee ◽  
ByungSik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hazard Ratio ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Grade Ii

Abstract Abstract 4177 Background Graft-versus-host disease (GVHD) is an immunologic complication after allogeneic hematopoietic stem cell transplantation (HSCT) with significant mortality and morbidities. Allogeneic peripheral blood stem cell transplantation (PBSCT) has high risk of GVHD, especially chronic GVHD compared to bone marrow transplantation. Only limited data are available comparing the efficacy of FK506 with that of cyclosporine (CsA) in human leukocyte antigen (HLA)-matched sibling PBSCT. Methods Thirty-nine patients with various hematologic disease received PBSCT with FK506+methotrexate (MTX) as GVHD prophylaxis were compared to ninety-four historical control with CsA+MTX GVHD prophylaxis. Results The 1-year cumulative incidence of grade II-IV acute GVHD was significantly lower in patients who received FK506 than those in the CsA group (10.3% vs 28.2%, p=0.036). The female donor-male recipient pair (hazard ratio; 4.828, 95% CI; 17.84-13.06, p=0.002) and CsA prophylaxis (hazard ratio; 3.279, 95% CI; 1.14–9.43, p=0.027) were significant risk factor of acute GVHD in multivariate analysis. But, there was no difference in the 3-year cumulative incidence of chronic GVHD between the FK506 and the CsA group (77.6% vs 69.6%, p=0.793). The 3-year cumulative incidence of relapse (33.9% vs 23.1%, p=0.505) and 3-year treatment-related mortality (18.9% vs 28.4%, p=0.187) of the two groups were similar. The patients in the FK506 arm had a similar event-free survival (EFS) and overall survival (OS) with patients in the CsA arm (3-year EFS; 53.2% vs 55.1%, p=0.706, 3-year OS; 60.7 vs 61.5%, p=0.610). The age over 35 years (hazard ratio; 4.12, 95% CI; 1.95–8.70, p=0.001), female donor-male recipient pair (hazard ratio; 2.66, 95% CI; 1.52–4.65, p=0.001) and advanced pre-HSCT disease status (hazard ratio; 3.13, 95% CI; 1.72–5.71, p=0.001) were significant prognostic factors associated with OS in multivariate analysis. Conclusion These results demonstrated that the FK506+MTX can significantly reduce grade II-IV acute GVHD compared to CsA+MTX in sibling PBSCT with similar incidence of chronic GVHD, and comparable outcome in EFS, OS, relapse rate and TRM rate between two groups. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Family Mismatched Donor Transplantation for Myelofibrosis: A Retrospective Analysis of the EBMT Chronic Leukaemia Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4655-4655 ◽  
Author(s):  
Kavita Raj ◽  
Eduardo Olavarria ◽  
Diderik-Jan Eikema ◽  
Liesbeth C de Wreede ◽  
Linda Koster ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Mismatched Donor

Abstract Background: Allogeneic stem cell transplantation is a treatment option for patients with advanced myelofibrosis. Problems encountered include an increased risk of delayed or poor engraftment and in the mismatched unrelated donor setting a higher rate of GVHD and particularly poor outcomes. As for other indications for allogeneic stem cell transplants, patients for whom either a matched sibling or matched unrelated donor is not available are considered for either a double umbilical cord blood, a mismatched unrelated donor or haploidentical stem cell transplant. Data on the latter option are limited and we reviewed registry data on all family mismatched donor transplants performed between 2001 and 2015 and reported to the EBMT registry. Results: Records retrieved 69 patients with myelofibrosis transplanted between November 2001 and November 2015. 44 (64%) were male. 50 (74%) had primary myelofibrosis,18 (27%) had secondary myelofibrosis (6 from ET, 5 from PRV and 7 others) and unknown 1(2%). Of 25 patients for whom the JAK2 V617F mutation status was known, 15 (22%) harboured the mutation. Patient Karnofsky performance status was > 70% in 98%. Of the mismatched family donors, 47 (68%) were male and 22 (31%) female. Donors were HLA mismatched at 1 locus in 12 (17%) and 2 or more loci in 48 (69%). Donor-recipient serology combinations were CMV -/- in 8 (12%), +/- in 4 (6%), -/+ in 15 (22%) and +/+ in 34 (49%) missing 8 (12%). Bone marrow was the stem cell source in 34 (49%) and peripheral blood in 35 (51%). The median total nucleated cell count (TNC) infused was 7.5x108/kg (range 2.3-21x108/kg) from data available in 17 patients. The median CD34+ cell dose was 6.9x106/kg (range 1.9-18.18x106/kg) from data available in 19 patients. Conditioning was myeloablative in 48 (70%) and RIC in 21 (30%) The conditioning regimes were varied but the predominant ones were Fludarabine, Busulphan, ATG (FBATG) and Thiotepa, Busulphan, Fludarabine (TBF). TBI was administered in 8 (12%) and in vivo T cell depletion in 22 (32%), ex-vivo T cell depletion in 5 (7%) patients. GVHD prophylaxis varied with post transplant Cyclophosphamide administered in 34/67 (49%) and ATG in 19/67 patients (28%). Neutrophil engraftment was established in 53 (82%) at a median of 20 days (range 11-83). Primary graft failure occurred in 8 (12%) and secondary graft failure in 4 (6%). This occurred at a median of 12 months (range 4.5-35 months). Eleven of these patients had a second allograft at a mean interval of 6.4 months. Responses to the first allograft (censoring for patients who had a second allograft) with data available in 45 patients, showed that complete remission was achieved in 35 patients (78%), 6 (13%) were never in CR and 4 (9%) were not evaluable. The cumulative incidence of grade II-IV acute GvHD at 100 days was 12% (95% CI 4-21%) and for grade III-IV acute GvHD at 100 days it was 5% (95% CI 3-11%). Data for chronic GVHD was valid in 49 patients. The cumulative incidence of chronic GvHD at 2 years was 62% (95% CI 47-76%). The cumulative incidence of limited cGvHD was 45% (95% CI 31-59%) whereas the cumulative incidence of extensive cGvHD was 10% (95% CI 2-19%). The median follow up was 24 months (95% CI 13-35 months). The 2-year OS was 51% (95% CI 37-76%) and the 5-year OS was 38% (95% CI 21-55%). The 2-year RFS was 44% (95% CI 30-59%) and the 5-year RFS was 31% (95% CI 15-48%). The 2 year cumulative incidence of relapse was 14% (95% CI 5-24%). The 2 year NRM was 41% (95% CI 28-55%), which increased to 54% (95% CI 37-72%) at 5 years. The main causes of death were infection (16, 24%), GVHD (7, 10%) organ damage or failure (3, 5%), relapse/disease progression (1, 2%) and secondary malignancy or PTLD (1, 2%). On univariate analysis there was no significant effect of recipient gender, donor gender, degree of HLA mismatch 1 vs >1 Ag MM, CMV matching between donor and recipient, primary or secondary MF, disease stage at transplant (chronic versus advanced phase), conditioning intensity, conditioning regimen, GVHD prophylaxis with ATG or post transplant cyclophosphamide or stem cell source on overall survival. Conclusion: Concerns regarding engraftment and secondary graft failure have excluded patients with myelofibrosis from clinical trials of mismatched related donor transplant. The data suggest that engraftment is feasible, and PFS and OS can be attained with limited severe chronic GVHD with family mismatched donors in this setting. Disclosures Ciceri: MolMed SpA: Consultancy.

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