Effect of Race on Outcomes After Allogeneic Hematopoietic Cell Transplantation for Severe Aplastic Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1020-1020
Author(s):  
Michael J Eckrich ◽  
Kwang W Ahn ◽  
Zhiwei Wang ◽  
H. Joachim Deeg ◽  
Mary M. Horowitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
African Americans ◽  
Aplastic Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Unrelated Donor ◽  
Matched Sibling ◽  
Overall Mortality

Abstract Abstract 1020 Severe aplastic anemia (SAA) is the most common non-malignant indication for hematopoietic cell transplantation (HCT). Although survival after HCT for SAA has improved in recent years, it is not known whether the observed higher survival rates are uniform across racial groups or whether there are differences similar to those seen with HCT for hematologic malignancies. Our primary objective was to compare overall survival after HCT for SAA in patients of African American and Caucasian races. The study population included patients who received HCT in the U.S. between 1990 and 2008. Eighty-four African Americans (cases) and 215 Caucasians (controls) were matched on factors known to be associated with survival after HCT for SAA, including age at HCT (±3 years), donor type (HLA-matched sibling, matched unrelated donor, mismatched unrelated donor), graft type (bone marrow or peripheral blood progenitor cells) and transplant year (±1 year). For 39 cases the match ratio for controls was 1:4, for 14 cases, 1:3, for 22 cases, 1:2 and the remaining 9 cases, 1:1. The median age of cases and controls was 17 years and the median interval from diagnosis to HCT was 3.4 months. Forty-five percent of transplants were from unrelated and 55% from HLA-matched sibling donors. A third of unrelated donor-recipient pairs were HLA-mismatched. Bone marrow was the predominant source of stem cells. The median follow-up of cases and controls was 5 years. In multivariate analysis, risk of overall mortality was higher for African Americans compared to Caucasians, relative risk [RR] 1.75, 95% CI 1.14–2.69, p=0.01. Risks of overall mortality were also higher during the early post-transplant period; odds ratio (OR) 2.42, 95% CI 1.09–5.37, p=0.03) and OR 2.61, 95% CI 1.33–5.47, p=0.005) at 3-months and 1-year post-transplantation, respectively. The 5-year probability of overall survival adjusted for interval from diagnosis to HCT, performance score and conditioning regimen, the other significant variables associated with higher mortality was 58% for African Americans and 73% for Caucasians. The likelihood of neutrophil recovery was similar in both groups (OR 1.03, 95% CI 0.46–2.33, p=0.94). Acute grades II–IV graft-versus-host disease (GVHD) risks did not differ between African Americans and Caucasians (RR 0.81, 95% CI 0.56–1.17, p=0.26). However, chronic GVHD risk was higher for African Americans, although the difference did not reach statistical significance (RR 1.55, 95% CI 0.98–2.44, p=0.06). Thirty-seven (45%) of 82 African Americans died compared to 56 (27%) of 207 Caucasians. The proportion of patients dying with GVHD was higher in African Americans (12 of 37; 32%) than among Caucasians (9 of 56; 16%). Death secondary to organ failure was higher in Caucasians (12 of 56; 26%) compared to African Americans (4 of 37; 11%). There were no differences between African Americans and Caucasian in regards to deaths from graft failure, infection or hemorrhage. These data suggest recent improvements in overall survival rates after HCT for SAA are largely limited to Caucasians. Higher mortality in African Americans may be explained by greater genetic diversity, which renders the identification of donors by high-resolution HLA-typing more challenging, genetic polymorphisms impacting drug metabolism and unmeasured co-morbidities. Novel strategies aimed at lowering acute and chronic GVHD rates are needed to lower GVHD-related deaths. Disclosures: No relevant conflicts of interest to declare.

Outcome of Alternative Donor Transplantation for Severe Aplastic Anemia Can Be Comparable to Outcome with Matched Related Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2052-2052
Author(s):  
Alana A. Kennedy-Nasser ◽  
Kathryn Leung ◽  
Steven Gottschalk ◽  
Dean A. Lee ◽  
George Carrum ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Aplastic Anemia ◽  
Pediatric Patients ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Alternative Donor

Abstract Matched related donor (MRD) bone marrow transplantation is the treatment of choice for pediatric patients with severe aplastic anemia; however, only 25% of patients will have an HLA-identical sibling. Alternative donor transplants may be an option for these patients, but such therapies have been associated with greater incidences of graft failures and graft-versus-host disease (GVHD). We retrospectively analyzed 32 pediatric patients who have undergone either bone marrow or peripheral blood stem cell transplant for severe aplastic anemia at our institution from April 1997 to April 2005. These patients had a total of 34 transplants. One patient had a MRD transplant followed by a matched unrelated donor (MUD) transplant eight years later, while another patient had a HLA-mismatched unrelated donor (MMUD) transplant followed by a transplant from a haplo-identical parent. Of the remaining 30 patients, 12 received MRD transplants, whereas 18 patients received alternative donor transplants - 11 MUD, 3 haplo-identical donors, and 4 MMUD. The median age at transplant was 9 years (range 1.5 to 18.4 yrs). All patients who received alternative donor transplants had previously failed therapy, including antithymocyte globulin (ATG) and cyclosporine. For MRD transplants, the conditioning regimen most often utilized cyclophosphamide 50 mg/kg x 4 days and ATG 30 mg/kg x 3 days. For alternative donor transplants, the conditioning regimen most often utilized cyclophosphamide 50 mg/kg x 4 days, Campath 3–10 mg x 4 days (dependent upon patient’s weight) or ATG 30 mg/kg x 3 days, and TBI (single fraction 200 cGy for MUD; two fractions 200 cGy for MMUD). Alternative donor recipients who received ATG in their preparative regimen were transplanted between December 1997 and March 2001 (n=9), whereas patients who received Campath were treated between November 2001 and April 2005 (n=11). GVHD prophylaxis was either FK506 or cyclosporine +/− mini-methotrexate. The overall survival for MRD patients was 91.7% versus 80% for alternative donor patients at a median follow-up of 47 months (range 3 to 100 months). Of the 32 patients, there were 5 deaths: pulmonary failure with extensive, chronic GVHD (n=1); poor graft function with infection (n=1); and infection (n=3). For patients receiving alternative donor transplants, the overall survival for the Campath group was 81.8% vs. 77.8% in the ATG group. None of the Campath patients developed extensive, chronic GVHD compared to 3/9 ATG patients. In conclusion, alternative donor transplantation using Campath or ATG in the preparatory regimens can establish donor engraftment and offers a curative therapy for pediatric severe aplastic anemia patients with survival similar to that of patients receiving matched sibling transplants. Although follow-up is shorter, Campath may be associated with a reduced incidence of extensive, chronic GVHD and further investigation is warranted.

scholarly journals Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1397-1400 ◽  
Author(s):  
Hubert Schrezenmeier ◽  
Jakob R. Passweg ◽  
Judith C. W. Marsh ◽  
Andrea Bacigalupo ◽  
Christopher N. Bredeson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Young Patients ◽  
Graft Versus Host ◽  
Sibling Donor ◽  
Peripheral Blood Progenitor Cells ◽  
Matched Sibling ◽  
Overall Mortality

AbstractWe analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versus-host disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P = .002) and overall mortality (RR 2.04; P = .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLA-matched sibling donor transplantation for SAA.

scholarly journals Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2354-2363 ◽  
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.

Unrelated Donor Hematopoietic Cell Transplant (HCT) for Hemophagocytic Lymphohistiocytosis (HLH).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 174-174 ◽  
Author(s):  
K. Scott Baker ◽  
Mary Eapen ◽  
Thomas Gross ◽  
Gregory A. Hale ◽  
Robert Hayashi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Systemic Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Early Mortality ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Peripheral Blood Stem Cells ◽  
Disease Specific ◽  
Overall Mortality

Abstract HLH is a rare immunoregulatory disorder characterized by widespread infiltration of histiocytes and T cells into organs, including the central nervous system (CNS), and is fatal in most cases without HCT. HLH can be inherited in an autosomal recessive pattern with unaffected sibling donors available for fewer than 20% of patients thus necessitating alternative donor HCT in the majority of cases. Data on 91 patients who underwent unrelated donor HCT and reported to the Center for International Blood and Marrow Transplant Research between 1989–2005 were analyzed. Fifty-one percent of patients were <1 yr at HCT and 29% had a Lansky performance score ≤80%. In a subset of patients (n=51) additional disease specific characteristics were available: 8 had a family history of HLH, of patients tested, 19 were confirmed to have either a perforin or MUNC-13 gene mutation; CNS disease was present at diagnosis in 21 patients and remained active in 4 at HCT; and 5 patients had active systemic disease at HCT. Most patients (80%) were conditioned with busulfan (BU), cyclophosphamide (CY), and etoposide (VP16) with or without anti-thymocyte globulin. Graft sources were bone marrow (86%), peripheral blood stem cells (4%) and cord blood (10%). Graft vs. host disease (GVHD) prophylaxis was cyclosporine or tacrolimus based in 89% of patients and T-cell depletion in 11%. Fifty-nine percent of grafts were matched at HLA A, B and DRB1, 34%, mismatched at 1-locus and 7%, mismatched at 2-loci. Neutrophil recovery was achieved by day 42 in 91% of patients. The probabilities of grades 2–4 acute at day-100 and chronic GVHD at 3-years were 41% and 23%, respectively. In multivariate analysis, the risk of overall mortality was 2-fold higher in patients who did not receive BU/CY/VP16 as their conditioning regimen (RR 1.99, p=0.03). In the sub-set of patients from whom disease-specific characteristics were available, overall mortality was higher in those with active systemic disease at HCT (RR 3.11, p=0.04). Early mortality was high, 35% at day-100 after HCT. Causes of early mortality included GVHD (n=5), infections (n=8), interstitial pneumonitis (n=8), organ failure (n=6), hemorrhage (n=3) and persistent disease (n=2). With a median follow-up of 49 months (range, 5–145) the 1- and 3-year probabilities of overall survival were 52% and 47%, respectively. For 46 patients with documented systemic remission at HCT, the 1- and 3-year probabilities of overall survival were 56% and 49%, respectively. These data represent the largest experience with unrelated donor HCT for HLH and demonstrate that a BU/CY/VP16 conditioning regimen provides cure in over 50% of patients. Outcome of HCT for patients with active systemic disease was poor with only 1 of 5 such patients surviving, demonstrating a need for novel therapies in patients who fail to respond to standard pre-transplant treatment. Unrelated donor HCT for HLH was associated with high early mortality and future studies should explore strategies to decrease early HCT-related mortality.

Low CD34 Cell Dose Is Associated With Higher Non-Relapse and Overall Mortality After Reduced Intensity Conditioning Hematopoietic Cell Transplantation For Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3342-3342
Author(s):  
Johan Thörlén ◽  
Olle Ringdén ◽  
Jennifer Le Rademacher ◽  
Minoo Battiwalla ◽  
Junfang Chen ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Disease Recurrence ◽  
Unrelated Donor ◽  
Performance Score ◽  
Cell Dose ◽  
Peripheral Blood Progenitor Cells ◽  
Matched Sibling ◽  
Overall Mortality

Abstract In allogeneic hematopoetic cell transplantation (HCT) using myeloablative conditioning, the nucleated and CD34 cell doses were found to be of importance for several outcome parameters including survival, relapse and graft- versus- host disease (GVHD). Reduced intensity conditioning (RIC) HCT is increasingly used for older patients and for younger patients with co-morbidities. Peripheral blood progenitor cells (PBPC) is the predominant graft for RIC HCT. There is no large study of the effect of CD34 cell dose in the setting of RIC transplantation. Therefore, we studied the effect of CD34 dose on 1057 patients aged 45 – 75 years with acute myeloid leukemia (AML) or myelodysplasic syndrome (MDS) who received RIC regimen HCT between 2000 and 2011. Patients received grafts from HLA-matched siblings (n = 370) or from volunteer adult unrelated donors matched at the allele-level at HLA-A, -B, -C and –DRB1 (8/8; n = 522) or mismatched at 1 HLA-locus (7/8; n = 178). All patients received peripheral blood progenitor cells (PBPC), low dose TBI regimens (200 cGy) or alkylating agent plus fludarabine containing regimens. Separate analyses were conducted for HLA-matched and unrelated donor transplants. For HLA-matched sibling transplants (AML n=301; MDS n=69), exploratory analysis identified differences in survival for CD34 dose less than 4 x 106/kg. Multivariate modeling, adjusting for performance score, disease status, cytogenetic risk and transplant period, showed transplantation of PBPC with CD34 dose < 4 x 106/kg was associated with higher risks of overall mortality (HR 1.48, p=0.008) and non-relapse mortality (HR 2.03, p=0.004) compared to transplantation of PBPC with CD34 dose ≥ 4 x 106/kg. The effect of CD34 dose was independent of the other factors associated with mortality. The likelihood of neutrophil (HR 0.76, p=0.03) and platelet recovery (HR 0.76, p=0.03) was also lower with CD34 dose < 4 x 106/kg containing PBPC grafts. CD34 dose was not associated with acute or chronic GVHD or disease recurrence. In contrast, after unrelated donor transplantation (AML n=557; MDS n=130), the effect of CD34 cell dose on mortality was marginal. Exploratory analysis identified differences in survival for CD34 dose less than 6 x 106/kg. After adjusting for age, performance score, disease status, interval from diagnosis to HCT, and HLA-match, transplantation of PBPC with CD34 dose < 6 x 106/kg was associated with marginally higher risks for overall mortality (HR 1.20, p=0.05) and non-relapse mortality (HR 1.38, p=0.02) compared to transplantation of PBPC with CD34 dose ≥ 6 x 106/kg. There were no significant differences in hematopoietic recovery, acute or chronic GVHD and disease recurrence by CD34 dose. Further, we did not identify a CD34 dose for either donor source above which acute or chronic GVHD risks were higher. In conclusion, in the setting of RIC transplants for AML and MDS, the data support optimizing PBPC collections such that the CD34 dose delivered is in excess of 4 x 106/kg for HLA-matched sibling and CD34 dose in excess of 6 x 106/kg for unrelated donor transplants. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Cell Transplantation for Acute Myelogenous Leukemia in Remission - a Prospective Comparison of Three Different Donor Groups; Matched Sibling, Matched Unrelated, and Haploidentical Family Donors

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4379-4379 ◽  
Author(s):  
Kyoo-Hyung Lee ◽  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Dae-Young Kim ◽  
Han-Seung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Acute Myelogenous Leukemia ◽  
Graft Failure ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
Matched Sibling

Abstract Allogeneic hematopoietic cell transplantation (HCT) from HLA-matched sibling (MS) or unrelated donors (MU) is a well-established treatment for patients with intermediate/high-risk acute myelogenous leukemia (AML) in remission. When HLA-matched donors are not available, however, use of haploidentical family (HF) donors for HCT remains controversial. Therefore, we performed a prospective study, where patients with AML in complete remission (CR) underwent allogeneic HCT according to the donor priority of MS, MU, or HF donors. Conditioning regimen for MS-HCT was busulfan (3.2 mg/kg • 4 days)-cyclophosphamide (60 mg/kg • 2 days) or, for patients >55 years or with co-morbidity, busulfan (3.2 mg/kg • 2 days)-fludarabine (30 mg/m2 • 6 days)-Thymoglobulin (1.5 mg/kg • 3 days). Patients undergoing MU- or HF-HCT received busulfan (3.2 mg/kg • 2 days)-fludarabine (30 mg/m2 • 6 days)-Thymoglobulin (3 mg/kg • 3 days) (Lee K-H et al; Blood 2011;118:2609-2617; Am J Hematol 2011;86:399-405). Ex-vivo T cell depletion was not performed. GVHD prophylaxis included cyclosporine plus a short course of methotrexate. Between January 2010 and December 2014, 244 patients enrolled. Of those, 16 patients were excluded from the analysis (12 patients relapsed before HCT; 3 with major protocol violation; and 1 with incomplete data). Of remaining 228 patients, 81 underwent HCT from MS donors, 90 from MU donors, and 57 from HF donors. The donors for MU-HCT were younger and more male-dominant than those for MS- or HF-HCT. The characteristics of patients and their donors were summarized in Table 1. Table 1. MS-HCT (n=81) UD-HCT (n=90) HF-HCT (n=57) P* Median age, yr (range) 48 (19-66) 43 (16-66) 46 (17-69) Sex, male/female 37/44 44/46 29/28 0.824 CR1/CR2 76/5 82/8 47/10 0.098 Chromosome risk,low**/intermediate/high/high-monosomal 6/57/10/5 4/65/16/3 2/40/7/5 0.751 Donor median age, yr (range) 45 (18-63) 28 (20-45) 29 (15-58) Donor age, yrup to 2526-45over 45 44136 29610 19326 0.000 Donor sex, male/female 46/35 76/14 36/21 0.000 Donor relation, parents/sibling/offspring 7/24/26 HLA allele mismatch/8 (GVH direction), 0/1/2/3/4 81/0/0/0 51/26/10/2/1 0/0/5/22/30 0.000 Graft, bone marrow/peripheral blood 28/53 0/90 0/57 0.000 Median nucleated cell count, •108/kg (range) 8.0 (0.9-19.0) 10.8 (4.1-31.4) 10.8 (5.1-19.3) Median CD34+ count, •106/kg (range) 4.9 (0.8-18.0) 8.0 (1.4-26.2) 6.4 (2.4-25.7) *by Chi-square test; **Twelve patients with AML of low-risk chromosomal abnormality included 6 patients in CR2, 3 with c-kit mutation, and 3 with persistent aml1-eto or cbf beta-myh11 after induction chemotherapy. The median follow-up duration of 164 survivors in the study was 34.7 months (range, 3.7-63.6) after HCT. The donor-group effect on the HCT outcomes was described in Table 2. Patients who underwent MS-HCT showed slightly slower neutrophil engraftment and higher incidence of chronic GVHD. Otherwise, in terms of disease recurrence, NRM, graft failure, EFS, and OS, there was no significant difference according to the donor-type. For AML recurrence, cytogenetic risk was an independent prognostic factors (P =0.003; hazard ratio of low-risk to; intermediate-risk, 1.42; high-risk, 2.53; high-risk with monosomal karyotype, 5.47). Table 1. MS-HCT (n=81) UD-HCT (n=90) HF-HCT (n=57) P Cumulative incidence ( 95% confidence interval)* AML recurrence 29% (19-40%) 26% (17-36%) 35% (20-51%) 0.785 Non-relapse mortality (NRM) 8% (3-16%) 7% (2%-16%) 11% (4-21%) 0.435 Graft failure 1% (0.1-6%) 6% (2-12%) 5% (1-13%) 0.293 ANC>500/uL median days (range) 100% 13 (9-20) 99%12 (10-45) 98% 12 (6-22) 0.049 Platelet>20,000/uL median days (range) 99% (86-100%) 14 (0-83) 97% (88-99%) 13 (0-77) 96% (83-99%) 14 (0-106) 0.352 Grades 2-4 acute graft-versus-host disease (GVHD) 12% (6-21%) 13% (7-21%) 23% (13-34%) 0.176 Moderate to severe chronic GVHD 39% (28-50%) 22% (13-30%) 23% (13-35%) 0.0452 4-year survival** Event-free (EFS) 63% 69% 54% 0.381 Overall (OS) 62% 74% 64% 0.077 *compared by Gray's method; **compared by log-rank test Our study showed that, despite heterogeneity of baseline donor characteristics (age and sex), conditioning regimen, and graft source (bone marrow vs. peripheral blood), overall post-transplant outcomes were similar among recipients from MS-, MU-, and HF-donors. Therefore, for patients with AML in CR but without an HLA-matched donor available, HCT from a haploidentical family member may be considered. Disclosures No relevant conflicts of interest to declare.

scholarly journals Baseline Body Mass Index Among Children and Adults Undergoing Allogeneic Hematopoietic Cell Transplantation: Clinical Characteristics and Outcomes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2558-2558
Author(s):  
Michael Gleimer ◽  
Yumeng Li ◽  
Lawrence Chang ◽  
Sophie Paczesny ◽  
David Hanauer ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
Overall Survival ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Normal Weight ◽  
P Value ◽  
Obese Patients

Abstract Obesity is a serious public health problem accompanying changes in diet and physical activity. The rising prevalence of obesity may influence the outcomes of hematopoietic cell transplantation (HCT). We studied 898 children and adults receiving first-time allogeneic bone marrow or peripheral blood stem cell transplants between 2004 and 2012 at the University of Michigan. Pre-transplant body mass index (BMI) was calculated using height and weight measurements and treated as a continuous variable. Recipients were then classified as underweight, normal weight, overweight, or obese according to BMI for adults using the World Health Organization classification system, or age-adjusted BMI percentiles for children based on Center for Disease Control and Prevention charts. The study population was predominantly Caucasian, and the median age was 51 years (5 months – 73 years). The cumulative 3-year incidence of non-relapse mortality (NRM) in underweight, normal weight, overweight, and obese patients was 20%, 19%, 20%, and 33% (p=0.04) (Figure 1A). Major causes of NRM were acute and chronic graft-versus-host disease (GVHD) (Figure 1B). The corresponding incidence of relapse was 30%, 41%, 37%, and 30% (p=0.002) (Figure 1C). Three-year overall survival was 59%, 48%, 47%, and 43% (p=0.55) (Figure 1D). Multivariate analysis showed that obesity was associated with higher NRM (hazard ratio [HR] 1.43, p=0.04), and lower relapse (HR 0.65, p=0.002) (Table 1). Pre-transplant plasma levels of ST2 and TNFR1 biomarkers were significantly higher in obese than in normal weight patients (p=0.04 and p=0.05, respectively) (Table 2). The increase in NRM observed in obese patients was partially offset by lower incidence of relapse, resulting in no significant difference in overall survival. Figure 1. Transplant outcomes according to BMI categories. Cumulative incidence of NRM (A), chronic GVHD (B), relapse (C), and probability of overall survival (D) according to BMI groups. N = 20 underweight (UW), 290 normal weight (NW), 287 overweight (OW), 301 obese (OB). Figure 1. Transplant outcomes according to BMI categories. Cumulative incidence of NRM (A), chronic GVHD (B), relapse (C), and probability of overall survival (D) according to BMI groups. N = 20 underweight (UW), 290 normal weight (NW), 287 overweight (OW), 301 obese (OB). Table 1. Results of multivariate regression analysis by BMI category. NRM Acute GVHD Chronic GVHD Relapse Overall survival Hazard ratio (95% confidence intervals), p value Normal weight 1.00 1.00 1.00 1.00 1.00 Underweight 1.74 (0.76−4.01), 0.19 1.11 (0.56−2.21), 0.76 0.99 (0.46−2.12), 0.98 0.70 (0.32−1.50), 0.36 1.02 (0.54−1.95), 0.95 Overweight 0.95 (0.65−1.37), 0.77 1.03 (0.78−1.35), 0.85 1.07 (0.83−1.38), 0.60 0.79 (0.61−1.03), 0.08 0.85 (0.68−1.07), 0.17 Obese 1.43 (1.02−2.01), 0.04 1.15 (0.89−1.50), 0.29 1.21 (0.94−1.55), 0.14 0.65 (0.49−0.86), 0.002 0.93 (0.75−1.16), 0.55 Other covariates Continuous age 1.01 (1.00−1.02), 0.18 1.00 (0.99−1.00), 0.37 1.00 (0.99−1.01), 0.69 1.00 (1.00−1.01), 0.36 1.01 (1.00−1.02), 0.003 Malignancy Non−malignant 1.00 1.00 1.00 1.00 1.00 Malignant 0.37 (0.10−1.33), 0.13 1.73 (0.82−3.68), 0.15 1.29 (0.72−2.31), 0.38 26.50 (3.49−201.02), 0.002 2.05 (0.92, 4.58), 0.08 Relatedness Related 1.00 1.00 1.00 1.00 1.00 Unrelated 2.20 (1.65−2.94), <0.001 1.88 (1.50−2.35), <0.001 1.13 (0.92−1.39), 0.23 0.61 (0.48−0.77), <0.001 1.24 (1.03−1.49), 0.02 Transplant type Peripheral blood 1.00 1.00 1.00 1.00 1.00 Bone marrow 0.23 (0.09−0.58), 0.002 0.66 (0.44−0.99), 0.04 0.91 (0.61−1.36), 0.65 1.09 (0.72−1.66), 0.68 0.56 (0.38−0.82), 0.003 HLA match Matched 1.00 1.00 1.00 1.00 1.00 Mismatched 1.59 (1.16−2.22), 0.004 1.69 (1.30−2.17), <0.001 0.95 (0.73−1.25), 0.73 0.83 (0.60−1.18), 0.29 1.41 (1.12−1.79), 0.003 Conditioning Myeloablative 1.00 1.00 1.00 1.00 1.00 Reduced 1.02 (0.76−1.35), 0.91 1.19 (0.94−1.49), 0.14 1.02 (0.82−1.27), 0.82 0.90 (0.69−1.16), 0.42 0.89 (0.74−1.09), 0.24 Year of transplant 2004−2008 1.00 1.00 1.00 1.00 1.00 2009−2013 0.79 (0.60−1.05), 0.10 0.76 (0.61−0.95), 0.02 0.96 (0.79−1.17), 0.70 0.76 (0.60−0.95), 0.02 0.78 (0.65−0.94), 0.01 Table 2. Baseline levels of plasma biomarkers suppression of tumorigenicity 2 (ST2) and tumor necrosis factor receptor 1 (TNFR1) by BMI category. ST2 TNFR1 BMI category N Median concentration (IQR), pg/ml p value N Median concentration (IQR), pg/ml p value Normal weight 115 131 (0-628) − 88 2129 (1486-3232) − Underweight 7 256 (82-659) 0.51 7 1596 (1467-2971) 0.57 Overweight 115 208 (0-845) 0.22 81 2266 (1708-3725) 0.32 Obese 110 257 (0-1045) 0.04 99 2644 (1922-3395) 0.05 Disclosures No relevant conflicts of interest to declare.

Comparable Survival and Transplant-Related Mortality Following Allogeneic Hematopoietic Cell Transplantation from HLA Allele-Matched Unrelated and HLA-Identical Sibling Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3146-3146 ◽  
Author(s):  
Thai M. Cao ◽  
Schickwann Tsai ◽  
Linda Kelley ◽  
Stephen C. Alder ◽  
Thomas C. Fuller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
P Value ◽  
Unrelated Donor ◽  
Related Mortality

Abstract Comprehensive analyses of unrelated donor (URD) and recipient HLA-matching for allogeneic hematopoietic cell transplantation (AHCT) have demonstrated better outcomes when allele typing is performed using high-resolution nucleotide sequence-based techniques. To evaluate survival following myeloablative AHCT using allele-level HLA-matched URD as compared with HLA-identical sibling donors, we analyzed outcomes for 430 patients treated at our center between March 1991 and April 2005. Sequence-based allele typing was retrospectively performed for HLA-A, B, C, DR and DQ when not done at time of AHCT for URD (n = 124; 29%) and non-sibling related donors (n = 19; 4%). Donors were HLA-identical siblings (n = 276; 64%), HLA allele-matched URD (n = 52; 12%), single HLA-locus mismatched donors (n = 52; 12%), or > 1 locus mismatched donors (n = 50; 12%). The median age at transplant was 23.4 years (range: 0.2 – 61). The most common diagnoses were AML (n = 107; 25%), CML (n = 90; 21%), ALL (n = 86; 20%) and MDS (n = 50; 12%). Total body irradiation-based preparative regimens were used for 283 patients (66%). Bone marrow (BM) was the graft for 388 patients (90%) and GCSF-mobilized peripheral blood stem cells (PBSC) for the remaining 42 (10%). Graft-versus-host disease (GVHD) prophylaxes were cyclosporine and methotrexate (n = 327; 76%), long methotrexate (n = 42; 10%), T-cell depletion (n = 19; 4%), or other regimens (n = 42; 10%). With a median follow-up of 4.8 years (range: 0.2 – 12.1), the 5-year estimate of overall survival (OS) for the entire group was 48.2% (95% CI: 45.7 – 50.7) and transplant-related mortality (TRM) was 31.4% (95% CI: 28.8 – 34). As shown in the Table, OS and TRM were indistinguishable between AHCT performed with HLA-identical siblings compared with HLA allele-matched URD. There was also no difference in grade III – IV acute GVHD (P = .46) between these two groups whereas there was a trend towards more extensive chronic GVHD (HR 1.8; 95% CI: 0.9 – 3.6; P = 0.12) for the URD recipients. Using a multivariate analysis to adjust for advanced disease, age (> vs ≤ 30 years), graft (BM vs PBSC) and female-to-male gender mismatch, there remained no difference in OS between HLA-identical siblings and HLA allele-matched URD (P = 0.67). These results demonstrate that key outcomes (OS, TRM, and severe acute GVHD) are equivalent in recipients of grafts from either allele-level 10/10 HLA-matched URD or HLA-identical siblings. Overall Survival TRM Number Hazard Ratio 95% CI P value Hazard Ratio95% CI P value HLA-ID Sibling 276 1 - - 1 - - HLA-ID URD 52 1.1 0.7 – 1.7 0.67 0.8 0.4 – 1.6 0.58 1 Locus MM 52 1.3 0.9 – 2.0 0.19 1.4 0.8 – 2.4 0.25 > 1 Locus MM 50 2.0 1.4 – 2.9 < 0.001 2.6 1.7 – 4.1 < 0.001

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

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1199-1199 ◽  
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.

Minor Histocompatibility Antigen Mismatch and Incidence of Graft Versus Host Disease, Event-Free, and Overall Survival in Patients Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4201-4201
Author(s):  
Brian C Shaffer ◽  
Christine Tremblay ◽  
Daniel Peaceman ◽  
Jennifer Hsu ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Graft Versus Host Disease ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Histocompatibility Antigen ◽  
Unrelated Donor ◽  
Minor Histocompatibility Antigen ◽  
Graft Versus Host

Abstract Abstract 4201 Graft versus Host Disease (GvHD) is a potentially devastating complication of allogeneic hematopoietic cell transplantation (HCT) initiated in part due to donor-recipient disparities in immunoreactive proteins, or minor histocompatibility antigens (mHAgs). There are no established prognostic tools to predict which patients will get acute or chronic GvHD. Analysis of mHAg mismatch is a potential predictive tool for GvHD; however, previous studies attempting to establish a relationship between mHAg mismatch and GvHD have been largely equivocal. Here we tested the hypothesis that analysis of an expanded set of mHAgs for mismatch in the GvH direction can be predictive of acute or chronic GvHD by NIH criteria. We additionally analyzed event-free (EFS) and overall survival (OS) in the mHAg matched and mismatched subgroups. Recipient/donor pairs from 45 HLA-A, -B, -C, and DRB1 matched unrelated donor transplants from 2007–2011 were retrospectively typed for 19 mHAgs using an SSP-PCR typing kit (Minor Histocompatibility Antigen Typing Kit; Life Technologies, Carlsbad, CA). Genomic DNA was obtained from peripheral blood mononuclear cells. EFS and OS were estimated using the Kaplan-Meier method. The relationship between mismatch and acute or chronic GvHD was described using Fischer's Exact Test. Cumulative incidence of treatment related mortality (TRM) was calculated using the Gooley Method. Two patients expired of early TRM and were excluded from the GvHD analyses. The rate of acute GvHD grades II-IV was 6 of 14 in those without a mHAg mismatch and 21 of 29 in those with a mismatch (43% versus 72%, P = 0.062). The rate of chronic GvHD was 8 of 14 in those without a mismatch and 10 of 29 in those with a mismatch (53% versus 34%, P = 0.140). The presence of a mismatch did not significantly impact EFS (P = 0.42) or OS (P = 0.26). The cumulative incidence of TRM at 24 months post transplantation was greater in patients with a mismatch (36% versus 13%). Two year OS was superior in patients who were conditioned with alemtuzumab (N = 24) and had a lower degree of mismatch (0–1 mismatch = 72% versus 2+ mismatches = 38%, P = 0.038). This study suggests the possibility of a relationship between mHAg mismatch and acute GvHD and TRM. Further study using this expanded mHAg analysis on a larger cohort of individuals would more adequately define the potential benefit of mHAg mismatch analysis in the context of unrelated donor HCT. Disclosures: No relevant conflicts of interest to declare.

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