A Combination of Two Distinct in vitro Amplification Procedures for DNA Typing of HLA-DRB and -DQB1 Alleles

Summary:There is consensus that matching of unrelated donors (URD) and patients for HLA class II alleles improves the outcome of hematopoietic stem cell transplantation (HSCT). However, the significance of HLA class I allelic mismatches for transplant outcome is under discussion and reports on long-term effects like chronic graft-versus-host disease (GVHD) are rare. Thus, we investigated the association of human leukocyte antigen (HLA) class I allele mismatches and outcome in 144 patients given HSCT from URD who were matched for HLA-DRB1, DRB3/4/5, and DQB1 alleles. The risk of chronic GVHD was significantly increased in patients with class I mismatched donors, the mismatch either detected by low-or high-resolution typing. A single HLA class I allele mismatch significantly increased the risk of chronic GVHD in multivariate analysis. Overall survival was significantly reduced in patient/donor pairs with more than one-allele class I mismatch. Thus, selection of unrelated donors for transplantation should be based on high-resolution HLA class I typing.

Section: Hla Typing and Strategy For The Selection Of Donorsmentioning

confidence: 99%

Impact of HLA class I high-resolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors

Greinix

Faé

Schneider

et al. 2004

“…In the remaining 18 (46%) pairs, class II region compatibility was assessed by DRB1, DRB3, DRB5, DQB1 allele typing by hybridization of amplified DNA with ligation-based typing (LBT). 19 In addition, DRB1 and DQB1 alleles were analyzed by nucleotide sequencing of allele-specific amplified DNA. 19 …”

Section: Histocompatibility Studies and Donor Selectionmentioning

confidence: 99%

“…19 In addition, DRB1 and DQB1 alleles were analyzed by nucleotide sequencing of allele-specific amplified DNA. 19 …”

Section: Histocompatibility Studies and Donor Selectionmentioning

confidence: 99%

Leukemia-free survival and mortality in patients with refractory or relapsed acute leukemia given marrow transplants from sibling and unrelated donors

Greinix

Reiter

Keil

et al. 1998

Summary:Between April 1982 and February 1997 39 patients (24 male, 15 female) with refractory acute leukemia and a median age of 31 years (19-51 years) received allogeneic marrow grafts from an HLA-identical sibling (n = 27), HLA-identical unrelated donor (MUD; n = 10) or 1-antigen mismatched unrelated donor (n = 2). Twentyeight patients had acute myelogenous leukemia and 11 acute lymphoblastic leukemia. For conditioning most patients received total body irradiation combined with cyclophosphamide (n = 23) or etoposide (n = 7). For graft-versus-host disease prophylaxis patients received cyclosporin A (CsA) and methotrexate (MTX) (n = 20), MTX alone (n = 3), CsA and methylprednisone (n = 6), or CsA alone (n = 10), respectively. As of June 1997 probability of leukemia-free survival projected to 3 years after BMT was 14% for patients given sibling marrow grafts and 28% after MUD transplantation. Transplant-related mortality projected to 3 years was 32% after sibling and 37% after MUD marrow grafting. Although not significantly different, probability of relapse projected to 3 years after BMT was lower after MUD at 56% compared to 78% with sibling BMT. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a curative potential for patients with refractory leukemia and offers the chance of long-term disease-free survival for some patients. Keywords: poor risk acute leukemia; sibling and unrelated marrow transplantation With current chemotherapies 80% of patients with acute myelogenous leukemia (AML) and more than 80% of patients with acute lymphoblastic leukemia (ALL) below the age of 50 years achieve complete hematological remission (CR).

“…Since 1994, ligation based typing of HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5 and HLA-DQB1 alleles was performed as described elsewhere. 18 In addition, nucleotide sequencing analysis of HLA-DRB1 and HLA-DQB1 alleles was performed. 18 Donor and recipient were considered matched if they were identical at HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ loci.…”

Section: Hla Typing and Donor Selectionmentioning

confidence: 99%

“…18 In addition, nucleotide sequencing analysis of HLA-DRB1 and HLA-DQB1 alleles was performed. 18 Donor and recipient were considered matched if they were identical at HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ loci. Donors were accepted if they were either fully matched or if there was a one-antigen mismatch.…”

Section: Hla Typing and Donor Selectionmentioning

confidence: 99%

Low transplant-related mortality in patients receiving unrelated donor marrow grafts for leukemia

Kalhs

Brugger

Reiter

et al. 1999

Summary:Transplantation with unrelated donor (UD) marrow has been shown to potentially cure patients with leukemia. Between January 1991 and April 1998, 54 patients with leukemia have received an UD BMT at our institution. Five patients received their UD BMT as a second transplant after a preceding autologous or syngeneic BMT and were excluded from further analysis. Forty-nine patients with leukemia (acute leukemia n ‫؍‬ 26; CML n ‫؍‬ 23) and a median age of 36 years (range 19-51) were analyzed. For conditioning, all patients received a combination of fractionated TBI and CY. GVHD prophylaxis consisted of MTX and CsA in all patients. As of 30 April 1998, 27 of 49 (55%) patients survive after a median observation time of 18 months. The probability of overall survival for standard risk and high risk patients is 54% and 31% (P ‫؍‬ 0.05). Probability of transplant-related mortality (TRM) is 27%, 24% in standard risk and 31% in high risk patients (P ‫؍‬ 0.44). Patients younger than 40 years (n ‫؍‬ 33) had a similar TRM as patients 40 years and older (n ‫؍‬ 16). The probability of relapse is 41% for the whole group, 29% for standard risk and 55% for high risk pts (P Ͻ 0.05). Our data confirm that UD BMT is an effective treatment for patients with leukemia. TRM is almost similar to related sibling BMT, most probably due to improvements in HLA typing technology, conditioning regimen and supportive patient care.