Reduced Relapse and Similar Progression-Free Survival After Double Umbilical Cord Blood Transplantation (DUCBT): Comparison of Outcomes Between Sibling, Unrelated Adult and Unrelated DUCB Hematopoietic Stem Cell (HSC) Donors.

Abstract Abstract 662 For patients with hematologic malignancies who lack a matched or mismatched unrelated donor, UCBT is an alternative. However, only a minority of larger adolescents and adults are able to find a single UCB with an adequate cell dose. Double UCB unit grafts (DUCB) have previously been shown to extend this HSC option. In order to understand the relative merits of each HSC source, we combined the datasets at the University of Minnesota and Fred Hutchinson Cancer Research Center. Between 2001- and 2008, 536 patients with leukemia (AML, n=211; ALL, n=236; CML, n=70 and MDS, n=19) were transplanted with HSC from a matched sibling (SIB, n=204), 8/8- (MUD, n=152) or 7/8-HLA (MMUD, n=52) matched unrelated donor or DUCB (n=128). All patients received myeloablative conditioning with cyclophosphamide 120 mg/kg and total body irradiation 1200-1320cGy with fludarabine 75mg/m2administered prior to DUCB. All patients received GVHD immunosuppression with a calcineurin inhibitor and either methotrexate (SIB, MUD and MMUD) or mycophenolate mofetil (DUCB). While patient weight and sex distribution and proportion with standard risk disease (STD, AML and ALL in CR1-2, and CML in CP1) were similar, DUCB pts were younger (median age 25 yrs, SIB 40 yrs, MUD 31 yrs, MMUD 31 yrs; p<.01). The proportion of AML and ALL was similar among groups, although more CML patients received a MUD or MMUD. Recipient CMV seropositivity was lower among MUD (44%; SIB 58%; MMUD 60; DUCB 62%, p<.01). The median follow-up of survivors was 3.1 yrs (0.3-8.1). The univariate point estimates at the stated timepoints and multivariate outcomes are summarized in the Table.Outcomes after SIB vs. MUD vs. MMUD vs. DUCBSIB* Ref.MUD* RR (95%CI)MVA p-value†MMUD* RR (95%CI)MVA p-value†DUCB* RR (95%CI)MVA p-value†Neutrophil Recovery at day 4598% 1.097% 0.62 (0.50-0.78). . <0.0198% 0.63 (0.46-0.86). . <0.0187%; 0.29 (0.23-0.37). . <0.01Platelet Recovery at day 10086% 1.081% 0.83 (0.64-1.09). . 0.1875% 0.71 (0.48-1.04). . 0.0845% 0.22 (0.17-0.29). . <0.01Grade II-IV aGVHD at day 10065% 1.080% 1.68 (0.32-2.14). . <0.0185% 2.17 (1.46-3.23). . <0.0160% 1.01 (0.76-1.35). . 0.94cGVHD at 2 year47% 1.043% 1.04 (0.75-1.46). . 0.8048% 1.24 (0.77-2.0). . 0.3726% 0.73 (0.47-1.13). . 0.16TRM at 3 years24% 1.014% 0.92 (0.53-1.60). . 0.7627% 1.83 (0.97-3.42). .0.0634% 2.86 (1.81-4.51). . <0.01Relapse at 5 years43% 1.037% 0.83 (0.58-1.19). . 0.3235% 0.68 (0.39-1.20). . 0.1915% 0.27 (0.16-0.47). . <0.01PFS at 5 years33% 1.048% 0.83 (0.62-1.11). . 0.2038% 1.04 (0.70-1.53). . 0.8551% 1.00 (0.73-1.37). . 0.99*Results are shown as pointwise estimates, relative risk (RR) and the 95% confidence interval. SIB group was the reference (Ref) group for the multivariate analysis (MVA).†P-value shown relates to multivariate analysis. In summary, after a Cy/TBI based myeloablation, DUCB is associated with slower hematopoietic recovery compared to other HSC sources. While incidence of acute GVHD was similar to that observed after SIB, DUCB was associated with less acute and trend toward less chronic GVHD relative to unrelated donors. Despite reduced risk of GVHD after DUCBT, risk of relapse was remarkably low while TRM was elevated, resulting in similar PFS. In the absence of a SIB donor, using either MUD or DUCB yield encouraging PFS and are promising donor options. These results support a) the front line use of HLA 0-2 antigen mismatched DUCB in patients with hematological malignancy, b) development of new strategies to enhance hematopoietic recovery after DUCBT, potentially reducing the risk of TRM, c) studies to understand why relapse rates are reduced with DUCBT and d) quality of life assessments long term between HSC groups, as there appears to be less risk of acute and chronic GVHD after DUCBT. Disclosures: No relevant conflicts of interest to declare.

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Are Outcomes After Myeloablative Conditioning Regimen in Double Cord Blood Transplantation (UCBT) Better Than Single UCBT for Adults with Acute Leukemia in Remission?.

Blood ◽

10.1182/blood.v120.21.3083.3083 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3083-3083

Author(s):

Annalisa Ruggeri ◽

Henrique Bittencourt ◽

Guillermo Sanz ◽

Alessandro Rambaldi ◽

Ibrahim Yakoub-Agha ◽

...

Keyword(s):

Multivariate Analysis ◽

Acute Leukemia ◽

Conflicts Of Interest ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Myeloablative Conditioning ◽

Hematopoietic Stem ◽

Grade Ii ◽

Group 2

Abstract Abstract 3083 Allogeneic hematopoietic stem cell transplantation (HSCT) is indicated for patients (pts) with acute leukemia (AL) with poor-risk cytogenetics or refractoriness to chemotherapy. For adults requiring HSCT urgently, such as pts in first complete remission (CR1), a single (s) or double unit (d) UCBT is a valid stem cells source. In the sUCBT setting, type of conditioning regimen seems to be associated with better outcome (Sanz BMT 2012). With the aim to compare single vs double UCBT after myeloablative conditioning regimen (MAC) in a homogeneous series of pts, we analyzed 239 adults (>18years) with AL in CR1. Pts were transplanted with sUCBT (n=156) or dUCBT (n=83) from 2005–2011 in EBMT centers for ALL (n=101) and AML (n=138). Type of MAC was statistically associated with outcomes therefore pts were analyzed in 3 different groups: Group 1: pts receiving sUCBT with TBI-based+Cy (+Flu) (n=68) (performed in 42 transplant centers (TC)), Group 2: pts receiving sUCBT with Bu+Flu+Thiotepa (n=88) (performed in 23 TC) and Group 3: pts receiving dUCBT with Cy+TBI+Flu (n=83) (performed in 47 TC). No statistical differences were found among the 3 groups for pts and disease characteristics (diagnosis, risk, gender, weight, CMV status, year of UCBT and time from diagnosis to UCBT) however pts in group2 were older than in group1 and 3 (median age 38 vs 33 vs 31 years) (p=0.03). Cytogenetic at diagnosis was available for 176 pts, 39% of pts were classified in the intermediate risk and 56% in unfavorable risk group. Forty-two pts had t(9;22) and 26 FLT3/ITD mutation. No differences on cytogenetic were found among the 3 groups. Thirty one percent of CB units were identical to recipient or had 1 HLA disparity (antigen level typing for HLA-A and B and allelic level for DRB1) while 69% had 2–3 HLA disparities. There was no difference on HLA disparities among the 3 groups. Median infused TNC was 2.9×107/kg for group1, 3×107/kg for group2, and 3.7×107/kg for group3 (p=0.01) and median CD34 was 1.2×105/kg, 1.6×105/kg and 1.5×105/kg, respectively (p=0.32). ATG was part of conditioning regimen in 73% of pts. The use of ATG was different in the 3 groups (70%, 90% and 40% for group1, 2 and 3, respectively p<0.001). GVHD prophylaxis consisted either of CSA±MMF or CSA±steroids in 46% and 22% of pts, respectively. All groups had the same median follow-up time: 24 (range 3–74) months. For group1, group2 and group3, the cumulative incidence (CI) of 60 days neutrophil recovery was 82%, 89% and 87% (p=0.15), with median time of 27, 21 and 24 days, respectively (p<0.001). Chimerism analysis performed at day 100 showed full donor chimerism in 87% of pts (data available for 80% of pts who engrafted). No differences in chimerism status were found between the 3 groups (p=0.47). At day 100, CI of acute GVHD (grade II-IV) was 30% vs 20% vs 45% for group1, group2 and group3, respectively (p=0.001). Pts receiving a dUCBT who developed aGvHD (n=38), experienced mainly grade II aGvHD with skin involvement (grade II (n=25), grade III (n=10), grade IV (n=3)). CI of chronic GvHD at 1 year was 29%, with no differences in the incidence among the groups. At 1 year, CI of TRM was 44% for group1, 33% for group2 and 36% for group3 (p=0.46). In multivariate analysis, two factors were associated with higher TRM: diagnosis of ALL (p=0.048) and age>35 years (p=0.049). One-Hundred-six pts died and the causes of death were infection (n=38), GvHD (n=18), other transplant-related events (n=31) or relapse (n=18). CI of 2y relapse was 25% for group1, 18% for group2 and 16% for group3 (p=0.22). No factors were found to be associated with increase relapse incidence in multivariate analysis. The 2y probability of leukemia-free-survival (LFS) was 31% for group1 (sUCBT-TBI based), 48% for group2 (sUCBT-BuFluTT), and 47% for group3 (dUCBT) (p=0.03). No center effect was found for LFS. In multivariate analysis, use of sUCBT using TBI based MAC (HR=0.9, p=0.003), diagnosis of ALL (HR=0.69, p=0.04) and age>35years (HR=1.4, p=0.04) were independently associated with decreased LFS. In this retrospective based registry analysis, in the myeloablative setting for adults with AL in CR1, outcomes (TRM, RI and LFS) after dUCBT were not statistically different from sUCBT using iv-BuFluTT. However, compared to sUCBT using TBI-based MAC, dUCBT was associated with lower RI and better LFS rates. In the MAC setting, the combination of conditioning regimens and type of graft (single vs. double) may have different impact UCBT outcomes. Disclosures: No relevant conflicts of interest to declare.

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Comparable Outcomes after Hematopoietic Stem Cell Transplantation from Mother Donors and Matched Unrelated Donors in Patients with Hematopoietic Malignancies

Blood ◽

10.1182/blood-2018-99-113961 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3463-3463

Author(s):

Rui MA ◽

Xiao-Jun Huang ◽

Lan-Ping Xu ◽

Kaiyan Liu ◽

Xiaohui Zhang ◽

...

Keyword(s):

Multivariate Analysis ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Donor Selection ◽

Unrelated Donor ◽

Donor Group ◽

Hematopoietic Stem ◽

Hematopoietic Recovery ◽

Unrelated Donors ◽

Transplantation Outcomes

Abstract BACKGROUND Haploidentical donor (HID) transplantations have achieved comparable survival as HLA fully matched unrelated donor (URD) transplantations. However, previous studies usually consider the two donor sources as whole populations when making the comparison, although there are actually subgroups within each. Based on current knowledge regarding donor selection, offspring and sibling donors were prioritized over parental donors in unmanipulated haplo-transplant settings, and maternal donors were considered as "the worst donors" under the Beijing Protocol due to the increased probabilities of GVHD and inferior survival. To compare efficacies of "the worst" mother donors and URDs would help to acquire a further understanding on donor selection of HIDs versus URDs. PATIENTS AND METHODS 43 and 92 patients who underwent transplantations with URDs or mother donors from June 2012 to June 2015 were enrolled. Their transplantation outcomes, including hematopoietic recovery, acute and chronic GVHD, relapse, transplant related mortality (TRM), overall survival (OS) and leukemia-free survival (LFS) were compared. Univariate and multivariate analysis were performed to explore risk factors for transplantation outcomes. RESULTS Both 2-year OS and 2-year LFS were comparable between the mother donor group and the URD group (74.8% versus 72.9%, p=0.937 and 71.7% versus 67.0%, p=0.580). Higher incidences of grade 2 to 4 acute GVHD and chronic GVHD were observed in the mother donor group than that in the URD group (43.5% versus 14.0%, p=0.001 and 58.8% versus 37.1%, p=0.013), although incidences of grade 3 to 4 aGVHD were similar between groups (mother donor group: 12%, URD group: 7%, p=0.374). Multivariate analysis indicated increased rates of acute GVHD were associated with mother donor transplantations (HR ratio: 2.049, p=0.017) and chronic GVHD was related to lower dose of CD34 cells infused (HR ration: 1.834, p=0.035) and female to male donations (HR ration: 1.733, p=0.047). The 2-year cumulative incidences of relapse were significantly decreased in the mother-donor group (7.6% versus 20.9%, p=0.036). Incidences of relapse were associated with donor types (URD vs mother donor: HR ratio 2.524, p=0.035) and disease status before transplantation (CR1 vs other: HR ratio 0.201, p=0.001) in multivariate analysis. These two groups were comparable in hematopoietic recovery and TRM (mother donor group: 21.1%, URD group: 11.6%, p=0.173). CONCLUSIONS Our findings suggest that mother donor transplantations could achieve comparable survival to unrelated donor transplantations, and exhibited decreased rates of relapse but increased rates of GVHD under the Beijing Protocol. This study not only shed light on donor selection by using one modality (the Beijing Protocol) to answer the universal question of HIDs versus URDs, but was also of practical significance due to possible shortage of unrelated donors, sibling donors and other suitable HIDs, especially in contemporary China with the one family one kid policy. Disclosures No relevant conflicts of interest to declare.

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Comparison of Outcomes for Non-Myeloablative (NMA) and Myeloablative (MA) Conditioning for Adults with Acute Lymphoblastic Leukaemia (ALL) in First and Second Complete Remission (CR): a Center for International Blood and Marrow Transplant Research (CIBMTR) Analyisis.

Blood ◽

10.1182/blood.v114.22.872.872 ◽

2009 ◽

Vol 114 (22) ◽

pp. 872-872 ◽

Cited By ~ 3

Author(s):

David I. Marks ◽

Tao Wang ◽

Waleska S. Peréz ◽

Donald W. Bunjes ◽

John F. DiPersio ◽

...

Keyword(s):

Multivariate Analysis ◽

T Cell ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Cell Depletion ◽

Unrelated Donor ◽

Conditioning Group ◽

T Cell Depletion ◽

Hematopoietic Stem ◽

Donor Transplant

Abstract Abstract 872 The efficacy of reduced intensity or NMA conditioning for allogeneic hematopoietic stem cell transplantation (HCT) for adults with ALL is uncertain. Using CIBMTR data we compared the outcomes of 92 patients ≥16 years who had NMA conditioning with 1421 patients who had myeloablative conditioning (MC) for allografts using sibling and unrelated donors for ALL in CR1 or CR2. Conditioning in the NMA group included regimens containing busulfan ≤ 9 mg/kg (27), melphalan ≤ 150 mg/m2 (23) or low-dose total body irradiation (36) and others (7). The NMA conditioning group were older (median 45 vs. 28 years, p<0.001) and more received peripheral blood grafts (73% vs. 43%, p<0.001). Other major potential prognostic factors were similar in the two groups. After a median follow-up of 54 vs. 38 months respectively, the NMA vs. MA conditioning groups had slightly less acute grade 2-4 graft-vs-host-disease (GVHD), less chronic GVHD but similar transplant-related mortality (TRM). However the NMA conditioning group experienced slightly more relapse (35% vs. 26%, p=0.08) yet similar overall survival (OS) (Figure): Outcome:MANMAP-value Acute GVHD @ 100 days, grades (2-4)46 (43-49)39 (29-49)0.16 Chronic GVHD @ 3 years42 (39-44)34 (24-44)0.16 TRM @ 3 years, %33 (31-36)32 (23-43)0.86 Relapse @ 3 years, %26 (23-38)35 (25-46)0.08 Leukemia-free survival (LFS) @ 3 years, %41 (38-44)32 (22-43)0.12 OS @ 3 years, %43 (40-46)38 (28-49)0.39 Multivariate analysis showed that a low Karnofsky score (KPS) and T cell depletion were associated with higher TRM but conditioning intensity had no impact on TRM (RR with NMA 0.97, P=0.89). Relapse risk with NMA conditioning was slightly, but not significantly higher ( (RR)=1.34, p=0.15) as was a CR2, particularly with a short (<12 months) initial CR (RR=2.74; longer remission (12 months) RR1.51, P<0.0001). Multivariate analysis demonstrated significantly improved OS with: KPS>80, CR1, lower WBC, no extramedullary disease, a well matched unrelated or a sibling donor, transplant since 2001, in younger patients (<30y), conditioning without TBI and GVHD prophylaxis without T-cell depletion. However ATG use did not affect survival.. The most common cause of death was relapse; which was similar in MA and NMA HCT (46% vs. 35%). Despite the older age in the NMA group, OS and LFS at 3 years was similar to those receiving MA HCT. In comparing the outcomes of NMA and MA conditioning in sibling vs. unrelated donor transplant recipients we found that there was slightly, but not significantly more relapse with NMA [34 (18-52)% vs. 26 (23-30)%, p=NS and 36 (24-49)% vs. 25 (22-28)%, p=NS respectively]. This was associated with similar OS of 40 (23-59)% vs. 50 (45-54)% and 37 (25-50) vs. 38 (34-41)% in the sibling and unrelated donor groups. Conclusions: These data suggest that NMA conditioning is worthy of investigation in prospective clinical trials of adult ALL. These trials should include both well matched unrelated and related donors, but importantly, NMA conditioning may not fully overcome the adverse impact of poor pre-HCT KPS on outcome. >Disclosures: No relevant conflicts of interest to declare.

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Partially Matched Related Donor Transplantation Can Achieve Outcomes Comparable to Unrelated Donor Transplantation for Patients with Hematologic Malignancies.

Blood ◽

10.1182/blood.v114.22.1197.1197 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1197-1197

Author(s):

Xiao Jun Huang ◽

Lan-Ping Xu ◽

Kai yan Liu ◽

Dai-Hong Liu ◽

Yu Wang ◽

...

Keyword(s):

Conflicts Of Interest ◽

Chronic Gvhd ◽

Hematologic Malignancies ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Free Survival ◽

Time Period ◽

Unrelated Donors ◽

Related Donor

Abstract Abstract 1197 Poster Board I-219 Abstract Purpose: To compare the outcomes of patients undergoing hematopoietic stem cell transplantation (HSCT) from partially matched related donors (PMRDs) or unrelated donors (URDs) for hematologic malignancies without the use of in vitro T cell depletion (TCD). Experimental Design: 297 consecutive patients were performed HSCT from URDs (n = 78) or PMRDs (n = 219) during the same time period. Incidences of graft-versus-host disease (GVHD), relapse, non-relapse mortality (NRM), overall survival (OS) and leukemia-free survival (LFS) are compared between the PMRD and URD groups. Results: All patients achieved full engraftment. The cumulative incidences of grades II to IV acute GVHD in the PMRD and URD cohorts were 47% (95% CI, 33%-62%) versus 31% (CI, 20%-42%, P = .033), with a relative risk (RR) = 1.72 (1.01-2.94), P = .046. The incidence of chronic GVHD did not differ significantly between the two cohorts (P = .17). Two-year incidences of NRM and relapse were 20% (CI, 15%-26%) versus 18% (CI, 10%-27%), with P = 0.98, and 12% (CI, 8%-16%) versus 18% (CI, 10%-27%), with P = .12, for the PMRD versus URD cohort respectively. Four-year OS and LFS were 74% (CI, 67%-80%) versus 74% (CI, 62%-85%), with P = .98, and 67% (CI, 59%-75%) versus 61% (CI, 47%-74%), with P = .74, respectively. Conclusions: Our comparisons demonstrate that every major end point, including relapse, NRM, OS and LFS, was comparable between the PMRD and URD groups. Disclosures: No relevant conflicts of interest to declare.

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Alemtuzumab Reduces Chronic Graft Versus Host Disease (cGVHD) and Treatment Related Mortality (TRM) after Reduced Intensity Conditioning for AML and MDS.

Blood ◽

10.1182/blood.v110.11.1076.1076 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1076-1076 ◽

Cited By ~ 1

Author(s):

Koen van Besien ◽

Marcos de Lima ◽

Andrew Artz ◽

Betul Oran ◽

Wendy Stock ◽

...

Keyword(s):

Chronic Gvhd ◽

Progression Free Survival ◽

Patient Characteristics ◽

Cancer Center ◽

P Value ◽

Unrelated Donor ◽

Post Transplant ◽

Md Anderson

Abstract In vivo T-cell depletion with alemtuzumab has been used to reduce acute and chronic GVHD. In order to evaluate its overall effect on transplant outcomes in AML and MDS we compared 90 pts who received fludarabine/melphalan/alemtuzumab (FMA) conditioning and post-transplant tacrolimus at the University of Chicago, with 112 who received fludarabine/melphalan (FM) and post-transplant tacrolimus/methotrexate at MD Anderson Cancer Center. Pt and transplant characteristics were well balanced except for a higher proportion of MDS in the FM group. Median age, proportion unrelated donor tx and proportion high/intermediate and low risk by ASBMT criteria were balanced between the groups. With median follow up of 28 months in both groups, one year progression free survival and overall survival are identical. TRM is significantly higher after FM, but relapse is higher in FMA. 19/103 d 28 survivors after FM vs 7/84 after FMA developed gr III–IV acute GVHD (p=0.04). 46/77 d100 survivors after FM developed ext cGVHD vs 7/63 after FMA (p=0.0000). 43 patients remain alive after FM and 27 have ext cGVHD. 41 remain alive after FMA and 1 has ext cGVHD. Alemtuzumab results in a considerable reduction in acute and particularly chronic GVHD. TRM is reduced compared with standard GVHD prophylaxis. Low incidence of chronic GVHD and reduced TRM may be the major benefit of this strategy. Relapse rates are increased, because of reduced GVL effects or because of improved early survival of high risk patients. Other approaches are necessary for improving long term outcomes. Patient Characteristics and Outcome FMA FM P-value N 90 102 Age (range) 54 (22–74) 51 (17–77) 0.6 AML/MDS 13/77 29/83 0.04 MUD/related 42/48 59/63 0.5 High./Intermediate/LowRisk 48/13/28 76/10/26 0.12 Median Follow up mths (range) 28 (3–89) 28 (1–66) 0.07 TRM@ 100 days 13% + 7% 24% + 8% 0.04 TRM@ 1 year 30% + 12% 42% + 10% 0.04 Relapse @ 1 year 40% + 12% 26% + 10% 0.01 PFS @ 2 years 33% + 11% 37% + 9% 0.9 OS @ 2 year 42% + 11% 44% + 9% 0.5 AGVD gr III–IV 7/84 19/103 0.04 Ext cGVHD 7/63 46/77 0.0000 Ext cGVHD in survivors 1/41 27/43 0.0000

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Re-Exposure of Cord Blood (CB) to Non-Inherited Maternal HLA Antigens (NIMA) Improves Transplant Outcome in Patients (pts) with Hematologic Malignancies and May Reduce Relapse.

Blood ◽

10.1182/blood.v114.22.661.661 ◽

2009 ◽

Vol 114 (22) ◽

pp. 661-661

Author(s):

Jon J van Rood ◽

Cladd E Stevens ◽

Jacqueline Smits ◽

Carmelita Carrier ◽

Carol Carpenter ◽

...

Keyword(s):

Conflicts Of Interest ◽

Chronic Gvhd ◽

Hla Antigens ◽

Human Leukocyte ◽

Hematologic Malignancies ◽

Hematopoietic Stem ◽

Leukocyte Antigens ◽

Grade Ii ◽

The Impact ◽

Related Mortality

Abstract Abstract 661 CB hematopoietic stem cell transplantation (CBT) can be successful even if donor and recipient are not fully matched for human leukocyte antigens (HLA). This may result, at least in part, from tolerance-inducing events during pregnancy, but this concept has not been tested to date. Hence we analyzed the impact of fetal exposure to NIMA of the HLA-A, -B antigens or -DRB1 alleles on the outcome of 1121 pts with hematologic malignancies. All pts received single CB units provided by the NYBC, for treatment of ALL (N=451), AML (N=376), CML (N=116), MDS (N=79), other (N=99); 22% were transplanted in advanced stage. Median age was 9.7 years (range: 0.1-67); 29% of recipients were >16 years. Most pts (96%) received myeloablative cytoreduction. Sixty-two pts received fully matched grafts while 1059 received units mismatched (MM) for one or two HLA antigens. Of these, 79 (7%) had a MM antigen which was identical to a donor NIMA (Example: Pt: A1, A3; CBU: A1, A2; mother-CBU: A1, A3; A3 is NIMA). NIMA match was found in 25 recipients with one HLA MM and 54 of those with two MM. The NIMA match was identified after the transplant and was not used in unit selection. In multivariate analyses, NIMA matched transplants (NMTs), showed faster neutrophil recovery (RR=1.3, p=0.043), even for grafts with cell dose <3×107 (RR=1.6, p=0.053). There was no difference in the incidence of acute (grade II-IV) or chronic GvHD. 3-year relapse risk (cumulative incidence 22%) was reduced compared to 1 or 2 HLA MM no NIMA matched transplants, especially in pts with myelogenous malignancies given units with 1 HLA MM (RR=0.2, p=0.074). Further, 3-year transplant-related mortality was reduced (RR=0.7, p=0.034), particularly in pts ≥5 years old (RR=0.5, p=0.006), as was the 3-year overall mortality (RR= 0.7, p=0.029 and RR=0.6, p=0.015, respectively). As a result, in the NMTs, treatment failure (relapse or death) was significantly lower, particularly in pts ≥5 years (RR=0.7, p=0.019) and DFS was significantly improved (figure) and was similar to that of the 0 HLA MM group. These findings are the first indication that donor exposure to NIMA can improve post-transplant survival in unrelated CBT and might reduce relapse. We propose to include the NIMA of CB units in search algorithms. Thus, for pts lacking fully HLA matched grafts, HLA MM but NIMA matched CB units could be selected preferentially, since no adverse effects were seen. This strategy of selecting HLA MM grafts with optimal outcome effectively “expands” the current CB Inventory several-fold.Patient GroupNRR(95% Cl)p value0 MM360.5(0.3–0.8)0.0051 MM / NIMA Match180.4(0.2–0.9)0.0262 MM / NIMA Match400.8(0.5–1.2)0.3091 MM / No NIMA Match229reference group2 MM / No NIMA Match4871.1(0.9–1.3)0.365 Disclosures: No relevant conflicts of interest to declare.

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A Myeloablative Conditioning Regimen With Fludarabine Demonstrates Good Results In UCBT With Hematologic Malignancies, Especially Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v122.21.4575.4575 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4575-4575

Author(s):

Juan Tong ◽

Sun Zimin ◽

Liu Huilan ◽

Geng Liangquan ◽

Zheng Changcheng ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Hematologic Malignancies ◽

Good Survival ◽

Myeloablative Conditioning ◽

Blood Transplantation

Objectives We retrospectively analyzed the safety and efficacy of a myeloablative conditioning regimen without anti-thymocyte globulin (ATG) or total body irradiation (TBI) but with fludarabine (FLU) in unrelated cord blood transplantation (UCBT) for 30 patients with hematologic malignancies. Methods The myeloablative conditioning regimen consisted of FLU, busulfan (BU) and cyclophosphamide (CY). All of the patients received Cyclosporine (CSA) and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prophylaxis. Results With this conditioning regimen, we achieved high engraftment rates (96.7%) and rapid hematopoietic reconstitution. Acute GVHD occurred in 12 cases of the 29 engraftment patients (41.4%), and 6 cases (20.7%) were of grade III-IV. Chronic GVHD only occurred in 1 of 28 evaluable patients (3.6%). Twenty-three patients (76.7%) became infected, and 3 cases (10.0%) died of severe infections. Cytomegalovirus (CMV) reactivation occurred in 70.0% of the patients, but no CMV diseases were observed, nor did any patients die of CMV infection. The cumulative incidence of relapse (6.7%) was significantly reduced, and none of the acute lymphoblastic leukemia (ALL) patients relapsed. The 3-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 70.0%, respectively, representing satisfactory survival. The 3-year OS and EFS of the ALL patients was 75.0%. Discussion This conditioning regimen resulted in a high engraftment rate, rapid myeloid reconstruction and a low incidence of infection. Although there were many patients with high-risk disease and disease progression, the regimen resulted in low relapse rates and good survival. None of the ALL patients relapsed after UCBT, indicating that this conditioning regimen could be applied to more patients with ALL. Disclosures: No relevant conflicts of interest to declare.

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Favorable Results of Allo-HSCT from MRD in Patients with Myelofibrosis

Blood ◽

10.1182/blood.v124.21.5934.5934 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5934-5934

Author(s):

Miroslaw Markiewicz ◽

Monika Dzierzak-Mietla ◽

Patrycja Zielinska ◽

Agata Wieczorkiewicz-Kabut ◽

Sylwia Mizia ◽

...

Keyword(s):

Bone Marrow ◽

Collagen Type ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Graft Loss ◽

Chronic Phase ◽

Curative Treatment ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Post Transplant

Abstract Introduction: Myelofibrosis (MF), chronic myeloid malignancy associated with shortened survival, in majority of patients develops de novo as Primary MF, but also polycythemia vera (PV) or essential thrombocythemia (ET) may progress into post-PV or post-ET MF. Although management of MF includes several treatment options, the only potentially curative treatment approach in MF is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Aim of this study was to evaluate the results of allo-HSCT in patients with MF treated in Katowice, Poland. Material and Methods: 27 pts (14 male and 13 female) with median age 51 years (range 21–63) were treated with allo-HCT due to PMF (20), post-PV (4) or post-ET (3) MF. 11,7,11,26 and 41% of pts had DIPSS 0,1,2,3 and 4, respectively. Median bone marrow cellularity was 70% (10-100%), fibrosis was collagen-type (14 pts including 2 with osteosclerosis), reticulin (10) or it was not specified (3). Splenomegaly was present in all pts: 13-20 cm (14 pts), > 20 cm (13 pts). JAK2V617F point mutation was present in 18 pts. Karyotype was available in 14 pts: in 9 normal, in 5 with variable abnormalities. Median time from diagnosis to allo-HCT was 1.5 (0.4–9.5) years. 16 pts (59.3%) received cells from HLA-matched related donor (MRD), 11 pts (40.7%) from unrelated donor: 10/10 (9) or 9/10 (2) HLA-A,B,C,DR,DQ alleles matched. Reduced intensity conditioning (RIC) was used in 26 pts, 1 patient received myeloablative conditioning (MC). Sources of stem cells were: peripheral blood (21), bone marrow (4) and both (2). All pts but one had chronic phase of MF at time of transplantation. Results: 14/27 (52%) pts are alive at median 3.4 (0.4-5.4) years after allo-HSCT: 11/16(69%) from MRD and 3/11(27%) from MUD, p=0.032. Graft failure, graft loss or PRCA were observed in 3, 5 and 1 pt, respectively. Absolute neutrophil count >0.5×109/L and platelet count >50×109/L were achieved at median 16 and 28 days, respectively. 12/27 (44%) pts reached complete blood count of Hb>10 g/dl, Plt>100 G/l and WBC>3.5 G/l; 11 of them (92%) are alive. 6/27 (22%) pts remained either RBC or PLT transfusions dependent post-transplant; 3 of them (50%) died. 9/27 (33%) pts remained both RBC and PLT transfusion dependent and all of them died. JAK2V617F mutation was completely eradicated in 11/16 evaluated previously positive patients (69%), decreased in 4 (25%) and stable in 1(6%) pt. Acute graft-versus-host disease (aGVHD) III-IV developed in 5/27 (19%) and extensive chronic GVHD in 5/19 (26%) pts. Relapse occurred in 4 pts and was treated with subsequent second transplant (in 1 pt thereafter by 3-rd allo-HSCT). Spleen length decreased at median by 5 (0.3-9.2) cm. Out of 7 pts with initial collagen fibrosis who were evaluated post-transplant, 1 had no fibrosis, 5 reticulin type and only in 1 pt collagen fibrosis was stable. Out of 3 pts with initial reticulin fibrosis it disappeared in 2 and progressed to collagen type in 1. Causes of death were GVHD (5 pts: 3 aGVHD, 2 cGVHD) and pancytopenia with either infection (7 pts) or CNS hemorrhage (1 pt). Conclusions: Allo-HSCT, the only curative treatment of myelofibrosis, provides chance of long survival, regression of the disease (lower stage of fibrosis, JAK2V617F eradication) and improved quality of life (transfusion independency, decreased splenomegaly). Transfusion independency may indicate good outcome. Favorable results are observed after allo-HSCT from MRD. Disclosures No relevant conflicts of interest to declare.

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Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan

Blood ◽

10.1182/blood-2007-11-118893 ◽

2008 ◽

Vol 112 (6) ◽

pp. 2579-2582 ◽

Cited By ~ 29

Author(s):

Hiroto Narimatsu ◽

Shigesaburo Miyakoshi ◽

Takuhiro Yamaguchi ◽

Masahiro Kami ◽

Tomoko Matsumura ◽

...

Keyword(s):

Multivariate Analysis ◽

Cord Blood ◽

Graft Versus Host Disease ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Japanese Patients ◽

Hematologic Malignancies ◽

Host Disease ◽

Graft Versus Host ◽

Blood Transplantation

Abstract We have little information on chronic graft-versus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects.

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Haploidentical/Mismatched Hematopoietic Stem Cell Transplantation for Nonresponders to Immunosuppressive Therapy Compared with First-Line Rabbit Antithymocyte Immunoglobulin Treatment Against Acquired Severe Aplastic Anemia

Blood ◽

10.1182/blood.v126.23.5508.5508 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5508-5508

Author(s):

Limin Liu ◽

Xiuli Wang ◽

Song Jin ◽

Lin Hao ◽

Yanming Zhang ◽

...

Keyword(s):

Treatment Failure ◽

Immunosuppressive Therapy ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Similar Treatment ◽

Treatment Failure Rate ◽

Grade Ii ◽

Immunoglobulin Treatment

Abstract We treated 86 patients with SAA, 31 patients who failed to respond to previous therapy underwent haploidentical hematopoietic SCT (haplo-HSCT, n=26) or mismatched unrelated donor HSCT (MMUD-HSCT, n=5). The other 55 patients were treated with immunosuppressive therapy (IST). At 6 months post-treatment, the treatment failure rates of HSCT and IST groups were 19.35% and 29.09% (P=0.320). Hematopoietic recovery time was shorter in the HSCT group than IST group (P > 0.05). The estimated OS at 3 years was 79.2% ± 7.7% in HSCT group and 89.7% ± 4.4% in the IST group (P=0.058). The estimated failure-free survival (FFS) at 3 years was 79.2% ± 7.7% in the HSCT group and 62.9% ± 8.0% in the IST group (P=0.391). The estimated FFS at 3 years in SAA that had progressed from non-SAA (NSAA) of HSCT was 71.6% ± 14.0% and 16.7% ± 13.6% of IST (P=0.021). Within the HSCT group, 38.71% of the patients developed grade II-IV acute GVHD, and 18.52% of the patients experienced moderate-severe chronic GVHD. These results suggest that haplo-HSCT/MMUD-HSCT and IST have similar treatment failure rate, OS and FFS. haplo-HSCT/MMUD-HSCT might provide a better chance of FFS than IST for SAA that had progressed from NSAA. Disclosures No relevant conflicts of interest to declare.

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