Allogeneic Bone Marrow Transplantation From HLA Mismatched Family Donors in Children with Aplastic Anemia

Abstract Abstract 831 The first-line therapy for children with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-matched family donor, and immunosuppressive therapy (IST) is indicated for patients without HLA-matched family donors. While the standard therapy for children who fail to respond to IST is allogeneic HSCT from an HLA-matched unrelated donor, HSCT from an HLA-mismatched family donor has also been indicated. Compared with unrelated donors, an HLA-mismatched family donor has some advantages especially for children who need urgent transplantation. We analyzed the clinical outcome of 578 children (325 boys and 253 girls) with AA (age, <20 years) who received allogeneic BMT between 1990 and 2009 in Japan, and registered to the Transplant Registry Unified Management Program (TRUMP). The median age at transplantation was 11 years (0–19), and the donors were serological 6/6 HLA-matched related donors (MRD) (n = 312), 1 locus-mismatched related donor (1MMRD) (n = 44), 2–3 loci-mismatched related (haploidentical) donors (n = 9), and HLA-matched unrelated donors (MUD) (n = 213). Causes of deaths were as follows: acute graft-versus-host disease (GVHD) (n = 4), chronic GVHD (n = 4), acute respiratory distress syndrome (n = 2), severe hemorrhage (n = 7), engraftment failure (n = 5), infection (n = 18), idiopathic pneumonia (n = 8), organ failure (n = 19), secondary malignancy (n = 4), and others (n = 4). The probability of severe acute GVHD (grade III–IV) in patients transplanted from 1MMRD (26.9% ± 7.4%) was significantly higher than that in patients transplanted from MRD (4.9% ± 1.3%) (p < 0.001). The probability of 5-year overall survival (5y OS) of patients transplanted from 1MMRD (93.1% ± 3.9%) was comparable to that of patients transplanted from MRD (93.1% ± 1.5%) (p = not significant, NS), but it was significantly better than that of patients transplanted from haploidentical donors (66.7% ± 15.7%, p =.016) and MUD (79.0% ± 2.9%, p =.014). In the subgroup analysis of 1MMRD, no significant difference was observed between HLA class I-mismatched (n = 32) and class II-mismatched patients (n = 12) (5y OS; 93.8% ± 4.3% vs. 91.7% ± 8.0%, p = NS). Comparison of the survival outcome based on the transplant period (1990–1999 vs. 2000–2009) revealed that the probability of 5y OS of patients transplanted from 1MMRD was not significantly different (92.3% ± 5.2% (n = 26) vs. 94.4% ± 5.4% (n = 18), p = NS), while that of patients transplanted from MUD significantly improved in the same period as we reported previously (67.1% ± 5.5% (n = 73) vs. 86.1% ± 3.1% (n = 140), p =.001)(Yagasaki et al., Blood 2011). In multivariate analysis, haploidentical donors (p <.001), MUD (p <.001), age ≥ 10 years (p <.001), and transplant period (1990–1999 vs. 2000–2009, p =.006) were identified as independent covariates associated with unfavorable OS. In summary, our analysis revealed that an HLA-mismatched related donor, especially 1MMRD, could be selected as a donor candidate for children with AA who need urgent transplantation. 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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Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia

Blood ◽

10.1182/blood.v85.9.2354.bloodjournal8592354 ◽

1995 ◽

Vol 85 (9) ◽

pp. 2354-2363 ◽

Cited By ~ 98

Author(s):

J Casper ◽

B Camitta ◽

R Truitt ◽

LA Baxter-Lowe ◽

N Bunin ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Myeloid Leukemia ◽

Chronic Gvhd ◽

Allogeneic Bone Marrow Transplantation ◽

Myelogenous Leukemia ◽

Unrelated Donor ◽

Allogeneic Bone ◽

Significant Difference ◽

Matched Sibling

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T- cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.

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Transplant Outcome of Unrelated Hematopoietic Stem Cell Transplantation (HSCT) after Myelo-Ablative or Reduced Intensity Conditioning (RIC) for Chronic Lymphocytic Leukemia(CLL). A Study of EBMT Registry.

Blood ◽

10.1182/blood.v106.11.561.561 ◽

2005 ◽

Vol 106 (11) ◽

pp. 561-561 ◽

Cited By ~ 2

Author(s):

Mauricette Michallet ◽

Thomas Prebet ◽

Quoc-Hung Le ◽

Anne-Sophie Michallet ◽

Anja Van Biezen ◽

...

Keyword(s):

Chronic Gvhd ◽

Hla Matching ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Significant Difference ◽

Unrelated Donors ◽

Global Population ◽

Reduced Intensity ◽

Grade Iii

Abstract Place of allogeneic HSCT in the therapeutical strategy of CLL remains still controversial and unrelated allogeneic transplantation has to be better explored. This retrospective analysis concerned 214 patients (164 males and 50 females) who underwent allogeneic HSCT for CLL from unrelated donors (150 males and 64 females) and who were reported on EBMT registry. The median age was 49 years. Fifty two patients received bone marrow (BM) and 162 peripheral blood stem cells (PBSC) from 48 HLA mismatched and 166 HLA matched unrelated donors. Sex mismatch and ABO incompatibility were found in 33% and 52% of cases respectively. On 194 evaluated patients for conditioning, 80 received a myelo-ablative regimen, 114 a reduced intensity conditioning and a Total Boby Irradiation was performed in 70 cases. After transplant, 72 patients (37%) developed an acute GVHD grade II-IV (36% in BM patients and 37% in PBSC patients; 49% in myelo-ablative group and 28% in RIC group). On evaluated patients, a chronic GVHD was present in 61% of the patients (50% in BM patients and 67% in PBSC patients, 66% in myelo-ablative group and 63% in RIC group). With a median follow-up of 20 months, we found no significant difference for 3-year probability of Overall Survival between myelo-ablative group (59%, 46–76) and RIC group (48%, 37–63). No significant difference was observed when comparing BM and PBSC patients whatever the conditioning they received. OS was significantly better in HLA matched compared to HLA mismatched patients in RIC population (51% vs 36%, p=0.01) but not in myelo-ablative population. In multivariate analysis (table 1) studying pre and post transplantation factors, a significant impact of 2 variables, age and aGVHD (grade III-IV vs 0-I), was shown on OS for the global population, myelo-ablative and RIC groups. Other variables influenced also significantly the OS: HLA matching (global and RIC populations), sex matching (myelo-ablative and RIC), TBI (myelo-ablative group). Concerning BM and PBSC groups, we demonstrated the influence of age and aGVHD. In conclusion, besides the known influence of severe aGVHD on survival, this study points out the importance of age and HLA matching in allogeneic unrelated HSCT transplantation setting for CLL. No difference was found regarding conditioning regimen and further studies are needed to determine the most adequate regimen for this disease. Multivariate analyses Variables OS (HR) p Global population Age 1.04 (1-1.07) 0.05 HLA matching: yes vs no 0.44 (0.22-0.89) 0.02 aGVHD grade III-IV vs 0-I 1.37 (1.1-1.74) 0.01 Myelo-ablative group Age 1.07 (1-1.13) 0.04 Sex Mismatch: F to M vs F to F 6.26 (1.53-25.6) 0.01 TBI: yes vs no 16.3 (3.26-80.2) 0.0006 aGVHD grade III-IV vs 0-I 1.9 (1.18-3.06) 0.008 RIC group Age 1.05 (1-1.1) 0.05 HLA matching: yes vs no 0.28 (0.1-0.76) 0.01 Sex Mismatch M to F vs F to F 0.63 (0.42-0.96) 0.03 aGVHD grade III-IV vs 0-I 1.66 (1.16-2.39) 0.005 BM group Age 1.12 (1-1.24) 0.03 aGVHD grade III-IV vs 0-I 1.88 (1-1.36) 0.05 PBSC group aGVHD grade III-IV vs 0-I 1.38 (1.02-1.86) 0.03

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One Antigen HLA-Mismatched Related and 8/8 Allele Matched Unrelated Donors Are Associated with Similar Survival after Hematopoietic Cell Transplantation for Acute Leukemia.

Blood ◽

10.1182/blood.v112.11.965.965 ◽

2008 ◽

Vol 112 (11) ◽

pp. 965-965

Author(s):

David Valcarcel ◽

Fangyu Kan ◽

Tao Wang ◽

Stephanie J. Lee ◽

Stephen R Spellman ◽

...

Keyword(s):

Acute Gvhd ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Disease Free Survival ◽

Unrelated Donor ◽

Free Survival ◽

Gvhd Prophylaxis ◽

Unrelated Donors ◽

Related Donor ◽

Disease Free

Abstract Patients in need of an allogenetic hematopoietic cell transplant but who lack an HLA genotypically identical sibling donor, are faced with the decision to consider a single HLA antigen mismatched related donor, or a search for a suitable 8/8 matched unrelated donor. We compared the outcomes of adult patients (≥18 years old) receiving a transplant for the treatment of AML or ALL in first or second remission from either a one-antigen mismatched related donor (MMRD group, N=89) reported to the CIBMTR or an 8/8 HLA-A, B, C and DRB1 allele matched unrelated donor (UD group, N=700) facilitated by the NMDP between 1995–2005. MMRD group was typed by serological or DNA-based methods for HLA-A, -B and –DR with all results verified by lab report review. The UD group was retrospectively typed for HLA-A, B, C and DRB1 by high resolution typing methods. Most received myeloablative conditioning regimens (77%), calcineurin inhibitor-based GVHD prophylaxis (100%) and T cell replete grafts (100%). 13% received ATG with the conditioning regimen. Median follow-up was 54 and 38 months in the MMRD and UD groups, respectively. The MMRD group was younger (median age 35 vs 43, p=0.002), had more ALL patients with low-risk cytogenetics (43% vs 18%, p=0.005), had older donors (median age: 38 vs 34, p=0.047), were more likely to receive methotrexate for GVHD prophylaxis (89% vs 77%, p=0.014) and were more likely to be transplanted prior to 2001 (62% vs 24%; p<0.001). There were no differences in patient or donor gender, diagnosis, disease-status, cytogenetic-risk of AML, time from diagnosis to transplant, stem cell source, conditioning regimen, use of ATG and Karnofsky index. Univariate comparisons (MMRD vs. UD) showed: 3-year OS (42% vs 44%, p=0.647), 3-year DFS (41% vs 41%, p=0.931), 3-year TRM (39% vs 31%, p=0.136), 3-year incidence of relapse (20% vs 28%, p=0.094), grade III–IV acute GVHD by 100 days (22% vs. 15%, p=0.147), chronic GVHD by 1 year (35% vs 47%, p=0.029). All multivariate analyses were adjusted for patient and transplant characteristics and are shown in the table below. In summary, transplants utilizing one-antigen mismatched related and 8/8 allele-matched unrelated donors did not significantly differ in overall survival or disease free survival, but chronic GVHD was more frequent after UD transplantation. Outcome RR (MMRD vs. UD) 95% CI p-value Survival 0.99 0.73–1.34 0.94 Disease-free survival 1.06 0.80–1.41 0.69 Treatment related mortality 1.14 0.77–1.69 0.52 Relapse 0.81 0.50–1.30 0.38 Acute GVHD III–IV 1.53 0.91–2.57 0.11 Chronic GVHD 0.58 0.39–0.85 0.006

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Improved Outcome After Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation (RI-HCT) for Myelodysplastic Syndrome (MDS) Using Tacrolimus/Sirolimus-Based Gvhd Prophylaxis.

Blood ◽

10.1182/blood.v114.22.2771.2771 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2771-2771 ◽

Cited By ~ 1

Author(s):

Ryotaro Nakamura ◽

Joycelynne Palmer ◽

Pablo Parker ◽

Anthony Stein ◽

Tracey Stiller ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Gvhd Prophylaxis ◽

Significant Difference ◽

One Year ◽

The Impact ◽

Bone Marrow Blasts ◽

Improved Outcome

Abstract Abstract 2771 Poster Board II-747 We previously reported an encouraging result with RI-HCT for MDS (Bone Marrow Transplant 2007; 40:843-50) using flugarabine/melphalan conditioning and cyclosporine (CSA)/mycophenolate (MMF) as GVHD prophylaxis. In order to further improve upon the outcome in the RI-HCT setting, we initiated a series of clinical trials at City of Hope National Medical Center designed to evaluate the impact of tacrolimus (FK)/sirolimus (SIRO)-based GVHD prophylaxis. Here we report the combined, updated results from a consecutive case-series of 89 patients with MDS (including AML progressed from MDS) who underwent RI-HCT from 2000 to 2008 and received either CSA/MMF (n =44) or FK/SIRO (n=45)-based GVHD prophylaxis. All patients received fludarabine 125 mg/m2 plus melphalan 140 mg/m2 followed by an allogeneic HCT (peripheral blood: n=83, bone marrow: n=6) from an HLA-identical sibling (SIB: n=35) or unrelated donor (MUD: n=54). Additional ATG was given to 12 patients. For MUD transplants a short course of methotrexate was added to CSA/MMF or FK/SIRO. The median age was 59 years (range: 20-71) and 31 (35%) patients were female, 58 (65%) were male. Diagnoses at transplant were RA (n=21), RARS (n=1), RAEB/RAEBT (n=36), and AML from prior MDS (n=31). Cytogenetic risk was low in 15 (17%), intermediate in 37 (41.5%), high in 37 (41.5%) patients. By IPSS criteria (for MDS only), 2 patients had low, 24 had int-1, 20 had int-2, and 12 had high-risk MDS. Twenty-seven patients had therapy-related MDS including 14 with prior autologous HCT. The median follow-up time for surviving patients was 39 months (range: 24-68) for the CSA/MMF group and 17 months (range: 4-39) for the FK/SIRO group. All but two patients (1 in CSA/MMF, 1 in FK/SIRO) engrafted with the median neutrophil recovery at 15 days (range: 11-55). The baseline patient, disease and transplant characteristics were similar between CSA/MMF and FK/SIRO, except for an increased percentage of therap-related MDS in the CSA/MMF group (43% vs. 18%, p<0.01). The median donor chimerism by STR at day 30 post-transplant was 100% in both groups (p=0.6). FK/SIRO was associated with a significantly reduced one-year non-relapse mortality (NRM) (11.4%) compared with CSA/MMF (36.2%, p=0.01). This improvement in NRM translated into a trend for improved overall survival (81.4% vs. 52.3%, p=0.1) and disease-free survival (72.2% vs. 52.3%, p=0.08) at one year. While we observed no significant difference in acute GVHD grade II-IV between CSA/MMF and FK/SIRO, FK/SIRO was associated with a significant reduction in grade IV GVHD (0% versus 26%, p<0.01) and a trend for III-IV GVHD (31% vs. 55%, p=0.1). There was no significant difference in chronic GVHD between FK/SIRO (60%) and CSA/MMF (56%, p=0.8). In multivariate analysis, the use of FK/SIRO was independently associated with improved NRM after adjusted for donor type, therapy-related MDS, %bone marrow blasts, and HLA match status (Table). In conclusion, FK/SIRO-based GVHD prophylaxis was associated with an improved outcome after RI-HCT for MDS attributable to the reduced risk for severe acute GVHD.Variables for NRMHazard Ratio (95% CI)p-valueDe novo (n=62) Therapy-related (n=27)baseline 0.75 (0.31–1.89)0.55Sibling donor (n=35) Unrelated donor (n=54)baseline 2.17 (0.70–6.74)0.18Bone marrow blasts < or =10% (n=67) Bone marrow blasts >10% (n=22)baseline 2.13 (0.92–4.96)0.08HLA match (sibling donor or 10/10 MUD, n=72)HLA < mismatch MUD (<10/10 match, n=17)baseline 6.26 (2.11–18.55)0.001FK/SIRO (n=45) CSA/MMF (n=44)baseline 6.58 (2.15–20.14)0.001 Disclosures: Off Label Use: cyclosporine, cellcept, tacrolimus, sirolimus, and methotrexate for GVHD prophylaxis.

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Race as a Factor in Donor Selection and Survival of Children with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplant in Florida

10.22541/au.161800122.22940406/v1 ◽

2021 ◽

Author(s):

Biljana Horn ◽

Deepak Chellapandian ◽

Nikhil Lamba ◽

Gauri Sunkersett ◽

Jorge GalvezSilva ◽

...

Keyword(s):

Hematologic Malignancies ◽

Unrelated Donor ◽

Cell Transplant ◽

Hla Matching ◽

Hematopoietic Cell Transplant ◽

Hematopoietic Stem ◽

Significant Difference ◽

Related Donor ◽

The Impact ◽

To Receive

Background Previous studies have explored post-hematopoietic cell transplant (HCT) outcomes by race in adults; however, pediatric data addressing this topic are scarce. Procedure This retrospective registry study included 238 White (W) and 57 Black (B) children with hematologic malignancies (HM) receiving first allogeneic HCT between 2010 and 2019 in one of five Florida pediatric HCT centers. Results We found no differences between W and B children by transplant characteristics, other than donor type. There was a significant difference in use of HLA-mismatched donors (HLA-MMD) (53% W, 71% B, p=0.01). When comparing HLA-MMD use to fully HLA-matched donors, B had RR of 1.47 [95% CI 0.7-3] of receiving a mismatched unrelated donor (MMUD), RR of 2.34 [95% CI 1.2-4.4] of receiving a mismatched related donor (MMRD), and a RR of 1.9 [95% CI 0.99-3.6] of receiving a mismatched cord blood donor (MMCBD) HCT, respectively. There was no significant difference in the incidence of aGVHD (48% W, 35% B), p=0.1 or cGVHD (19% W 28% B, p=0.1), or primary cause of death. Overall 24-month survival was 61% [95% CI 54-68%] for W, and 60% [95% CI 38-68] for B children, log-rank p=0.72. While HLA matching improved survival in W children, the number of B children receiving HLA-matched HCT was too small to identify the impact of HLA matching on survival. Conclusions In this contemporary cohort of children with HM we found that B children were more likely to receive HLA-MMD transplants, but this did not adversely affect survival or GVHD rates.

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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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Single-Institute Comparable Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated and Related Donor in Patients with Myeloid Malignancies.

Blood ◽

10.1182/blood.v110.11.4946.4946 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4946-4946

Author(s):

Shingo Yano ◽

Noriko Usui ◽

Nobuaki Dobashi ◽

Yutaka Takei ◽

Yuichi Yahagi ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Myeloid Malignancies ◽

Related Donor

Abstract Background: Allogeneic stem-cell transplantation (allo-SCT) from human leukocyte antigen identical related donor (RD) is taken priority over unrelated donor (URD), however, less than 30% of patients do not have a suitable RD. Transplantation from an URD should be considered for those patients. In order to investigate the role of URD, we retrospectively analyzed efficacy and safety of allo-SCT from URD and RD in patients with myeloid malignancies. Patients and methods: One hundred six patients with myeloid malignancies (acute myeloid leukemia 48, chronic myeloid leukemia 38, and myelodysplastic syndrome 20) who received myeloablative regimens were analyzed. The stem cell source were bone marrow from URD (n=43) and peripheral blood stem cells or bone marrow from RD (n=63). Graft-versus-host disease (GVHD) prophylaxis consisted of taclorimus and short-term methotrexate (sMTX) for URD, or cyclosporine and sMTX for RD. Results: Median follow-up was 6.3 (0.3–17.2) years, and median age of patients was 37 (15–55) years old. Hematological studies demonstrated donor engraftment in all patients. Incidence of grades II to IV of acute GVHD was 32% in URD and 18% in RD, and extended chronic GVHD was 31% in URD and 28% in RD. Probability of 8-year actuarial survival was 62% in URD and 54% in RD (p=0.4225), and 8-year disease-free survival was 64% in URD and 47% in RD (p=0.1412). There were no apparent differences in transplant-related mortality (TRM) (14% in URD and 24% in RD), relapse (14% in URD and 32% in RD) between both groups. Conclusion: These results suggested that allo-SCT from URD has comparable safety and effectiveness for adult patients with myeloid malignancies.

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Impact of Missing KIR Ligands in HLA-Matched Unrelated Donor HSCT.

Blood ◽

10.1182/blood.v114.22.1185.1185 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1185-1185

Author(s):

Aining Sun ◽

Weiyang Li ◽

Wu Depei ◽

Jun He ◽

Xiaojing Bao ◽

...

Keyword(s):

Conflicts Of Interest ◽

Chronic Gvhd ◽

Hla Class I ◽

Unrelated Donor ◽

Prognostic Impact ◽

Matched Unrelated Donor ◽

Hematopoietic Stem ◽

Immunoglobulin Receptor ◽

Significant Difference ◽

Hla Genotype

Abstract Abstract 1185 Poster Board I-207 Objective: To analyze the prognostic impact of missing ligands for inhibitory killer-immunoglobulin receptor(KIR) in HLA-matched hematopoietic stem cell transplantation(HSCT) using unrelated donor. Methods: HLA genotype of 51 patients (ALL 22 cases, AML 13 cases, CML 14 cases, MDS 1 cases and HAL 1 cases) and their matched unrelated donors was determined by polymerase chain reaction sequence oligonucleotide probes(PCR-SSOP) and sequence specific primers (PCR-SSP). The KIR genotype was determined by PCR-SSP. Results: Patients were divided into those with(n=37) and those without(n=14) missing 1 or more HLA class I ligands for donor inhibitory KIR. The period of platelet reconstruction was shorter in patients [ 13 d(10d∼27d)] with missing KIR ligands than those[14d(12d∼21d)] without missing KIR ligands(P=0.046). There was no significant difference in neutrophil recovery, ≥II° acute GVHD(13.5% vs 35.7%, P>0.05) and extensive chronic GVHD (16.2% vs 28.6%, P>0.05) between the two groups. The 3-year continuous complete remission(CCR) rate for patients with and without missing KIR ligands was 73.6% and 37.4%, respectively(P=0.183). The 3-year overall survival(OS) rate for the two groups was 77.5% and 52.4%, respectively(P=0.533). Conclusions: In HLA-matched unrelated donor HSCT, missing KIR ligands may be associated with enhanced engraftment, decreased severe GVHD, improved CCR and OS. Disclosures: No relevant conflicts of interest to declare.

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Allogeneic Hematopoietic Cell Transplantation in AML: Comparable Results After Matched or Mismatched Unrelated Versus Matched Related Transplantation.

Blood ◽

10.1182/blood.v114.22.1199.1199 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1199-1199 ◽

Cited By ~ 1

Author(s):

Birgit Federmann ◽

Christoph Faul ◽

Wichard Vogel ◽

Lothar Kanz ◽

Wolfgang Andreas Bethge

Keyword(s):

Overall Survival ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Off Label Use ◽

Hematopoietic Stem ◽

Off Label ◽

Significant Difference ◽

Label Use

Abstract Abstract 1199 Poster Board I-221 Currently, most treatment algorithms reserve the use of allogeneic hematopoietic stem cell transplantation (HCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR) to patients with a matched related donor (MRD) and intermediate/high-risk disease. However, the role of HCT from a matched or mismatched unrelated donor (MUD/MMUD) in patients with AML remains to be defined. We retrospectively analyzed a cohort of 219 consecutive adult patients (98 female, 121 male) with AML who received HCT from 2000-2009 at our institution. The patients were transplanted after either myeloablative (MAC, n=139) or dose-reduced-conditioning regimens (RIC, n=80). Median age of patients was 50 years (range, 18-76). 77 patients were transplanted from MRD, 80 patients from MUD and 62 patients from MMUD (one antigen mismatch (MM)=31; two antigen MM=2; one allel MM=24; two allel MM=3, one antigen/one allel MM= 2). In all but six patients receiving MMUD grafts, ATG was included in the conditioning. Age, risk profile and pretreatment were evenly distributed among the three cohorts of patients. At time of HCT 22 (MRD), 18 (MUD) and 28 (MMUD) patients were not in CR. Current overall survival is 40 of 77 (52%) in patients transplanted from MRD, 48 of 80 (60%) from MUD and 34 of 62 (55%) from MMUD with a median follow-up of 1309 (range, 98-3173), 796 (range, 87-3075) and 648 (range, 111-1973) days of alive patients, respectively. Kaplan-Meier-estimated 3-year overall survival (OS) was similar with 54% after MRD-, 56% after MUD- and 46% after MMUD-HCT (p=0.4554). In patients transplanted in CR, 3-year estimated OS was also comparable (64% MRD vs. 58% MUD vs. 55% MMUD, p=0.6614). However, in patients transplanted in partial remission (PR) we observed a trend for a better survival in patients receiving a MUD graft (30% MRD vs. 46% MUD vs. 39% MMUD, p=0.1707). In the patients receiving MAC we observed a better OS compared to RIC with an estimated 3-year OS of 58% vs. 38% (p=0.1047) mainly due to a lower incidence of relapse. In the subgroup of patients receiving MRD-HCT this survival benefit was significant (61% vs. 21%, p= 0.0327) while there was only a trend for MUD- or MMUD-HCT (60% vs 45%, p=0.5702 and 49% vs. 43%, p= 0.7566, respectively). There was no significant difference in the incidence of acute GvHD >II with 25% (MRD), 35% (MUD) and 34% (MMUD) or chronic GvHD with 43% (MRD), 46% (MUD) and 34% (MMUD), respectively. A significant better survival of patients with limited cGvHD vs. extensive or without cGvHD (estimated 3-year OS 73% vs. 34% vs. 47%, p=0.0001) was observed. This advantage was present in all subgroups with a significant better survival in the group with MRD (86% vs. 38% p= 0.0034), a trend in MUD (67% vs. 55% p= 0.0564) and MMUD (59% vs. 55%, p= 0.3111). No significant influence on survival or GVHD of the degree and loci of HLA-mismatch could be detected. In conclusion in our cohort of patients, HCT from MUD or MMUD in AML resulted in a similar outcome compared to MRD. In patients with PR at time of HCT, the use of MUD and occurrence of limited cGVHD may lead to improved survival due to an enhanced graft-versus-leukemia-effect. Disclosures: Off Label Use: some chemotherapeutical agents in the conditioning are off-label-use.

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