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Post-transplantation cyclophosphamide (PTCy) can reduce the incidence of graft versus host disease (GVHD) and this intervention is often applied on adults with hematologic malignancy. However, the high relapse rate hinders the development of the intervention and data of PTCy used on children with hematologic malignancy remains limited. In order to overcome issue of high relapse rate in PTCy treatment, we used fludarabine (Flu), enhanced dose of cytarabine (Ara-C, 9 g/m2), busulfan (Bu), Cy, anti-thymocyte globulin (ATG) combined with PTCy for an intensified conditioning regimen. A total of 22 children with acute leukemia received intensified PTCy conditioning regimen (PTCy intensified group). We matched with 18 children who received modified Bu-Cy and ATG conditioning regimen in the same period (ATG group). The two-year cumulative incidences of grade II–IV acute GVHD was significantly lower in PTCy intensified group (13.6 ± 7.7% vs 38.9 ± 11.5%, P = 0.048). Two-year GVHD-free relapse free survival (GRFS) in PTCy seems to be better among the increment group despite not being significant (63.3 ± 10.3% vs 35.4 ± 11.9%, P = 0.092). The positive rate of minimal residual disease after transplantation was significantly lower than that before transplantation (20.0% vs 2.5%, P = 0.029). In conclusion, ATG and PTCy combined with Flu-based increased intensity conditioning regimen is effective for acute leukemia in children. It could reduce GVHD rate significantly and potentially improve GRFS. [ABSTRACT FROM AUTHOR]

Objective: HLA-C*15:29 is a low-frequency allele in the human leukocyte antigen (HLA)-C locus. The aim of this study is to confirm the ethnicity of C*15:29 and to deduce a probable HLA haplotype in association with C*15:29 in Taiwanese population. Materials and Methods: A total of 12,534 healthy unrelated Taiwanese individuals were tested for HLA using a sequence-based typing method. The DNA material was subjected to HLA genotyping for the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci using a commercial polymerase chain reaction–sequencing-based typing kit as per the manufacturer's protocols. Results: The DNA sequence of C*15:29 is identical to C*15:02:01:01 in exons 1, 2, 3, 4, 5, and 6 except for residues 420 and 1034 where A and G of C*15:02:01:01 are substituted by C and A in C*15:29, respectively. The nucleotide substitutions introduce two amino acid replacements at residues 116 and 321 where leucine (L) and cysteine (C) of C*15:02:01:01 are replaced by phenylalanine (F) and tyrosine (Y) in C*15:29, respectively. A probable HLA haplotype associated with C*15:29 in Taiwanese was deduced as A*29:01-B*07:05-C*15:29-DRB1*10:01-DQB1*05:01. The frequency of C*15:29 is estimated at about 0.064%. Conclusion: Information on the ethnicity and distribution of C*15:29 and its deduced probable HLA haplotype is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals. Materials and Methods: A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was performed to amplify exons 2, 3 and 4 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the *BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of B*40:247 is identical to B*40:01:01 in exons 2, 3 and 4 except for residue 853, where G of B*40:01:01 is changed to A in B*40:247 (codon 261, GTA->ATA). The nucleotide replacement causes a one amino acid change at codon 261 where V (valine) of B*40:01:01 is replaced by I (isoleucine) in B*40:247. We deduced the probable HLA haplotype associated with B*40:247 in Taiwanese to be HLA-A*24:02-B*40:247-C*03:04-DRB1*16:02. Conclusion: Information on the ethnicity and distribution of B*40:247 and its deduced probable HLA haplotype in association with the low incidence allele is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: Human leukocyte antigen (HLA)-DRB1*15:140 is a low-frequency allele in the HLA-DRB1 locus. The aim of this study is to confirm the ethnicity of DRB1*15:140 and to deduce a probable HLA-DRB1*15:140-associated HLA haplotype in Taiwanese individuals. Materials and Methods: A total of 1815 healthy unrelated Taiwanese individuals and 14,562 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exons 1 and 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of HLA-DRB1*15:140 is identical to DRB1*15:02:01:01 in exons 1 and 2, except at residue 91 of DRB1*15:02:01:01 where a G in DRB1*15:02:01:01 is replaced by an A in DRB1*15:140 (codon 2; GAC->AAC). The nucleotide substitution in exon 1 introduces a one amino acid substitution at residue 2 where an aspartic acid (D) in DRB1*15:02:01:01 is replaced by an asparagine (N) in DRB1*15:140. We deduced the probable HLA haplotype associated with DRB1*15:140 in Taiwanese to be HLA-A*33:03-B*58:01-DRB1*15:140. Conclusion: Information on the ethnicity and distribution of DRB1*15:140 and its deduced probable HLA haplotype in association with the low-incidence allele is of value for HLA-testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: Human leukocyte antigen (HLA) DRB1*04:36 is a low-frequency HLA-DRB1 allele. The aim here is to report the ethnicity of DRB1*04:36 and its associated HLA haplotypes among Taiwanese individuals. Materials and Methods: A sequence-based typing method was employed to confirm this low incidence allele. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. One group of unrelated blood donors used in this study consists of randomized individuals with Taiwanese ethnicity who participate in the Tzu Chi Bone Marrow Donor Registry and the other group are randomized unrelated individuals from mainland China. The family members in the family part of the study are volunteer blood donors. Results: In exon 2, the DNA sequence of DRB1*04:36 is identical to DRB1*04:03:01 except for a nucleotide segment from residue 286 to residue 308. The nucleotide segment from residue 286 to residue 308, incidentally, is identical to that of DRB1*11:01:01:01. These observations suggest that DRB1*04:36 may have been derived through a gene recombination event involving DRB1*04:03:01 and DRB1*11:01:01:01. Our family study indicated that the HLA haplotype in association with DRB1*04:36 can be deduced to be A*24:02-B*39:01-DRB1*04:36. A randomized population study using Taiwanese suggests that additional DRB1*04:36 associated HLA haplotypes seem to exist. Conclusion: The information on the ethnicity of the DRB1**04:36 allele, and the deduced probable HLA haplotypes associated with the low incidence DRB1*04:36 allele that we report here, is of value to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid the creation of strategy for finding compatible donors who are part of unrelated bone marrow donor registries when a patient carries this uncommon HLA allele.

Objective: HLA-A*11:256Q and HLA-A*02:621 are two low-frequency HLA-A alleles. The aim here is to report the ethnicity of A*11:256Q and A*02:621 and associated human leukocyte antigen (HLA) haplotypes among Taiwanese individuals. Materials and Methods: HLA data from randomized Taiwanese registered in the Tzu Chi Stem Cells Centre and China Shanghai Tissuebank Diagnostics were analyzed. HLA typing of the donors was carried out using a sequence-based typing method to confirm the two low-incidence alleles. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. Exon 1 and exons 4-8 of the A*11:256Q allele were also sequenced and analyzed. Results: The Taiwanese ethnicity for both A*11:256Q and A*02:621 alleles was confirmed in this study. Further, the DNA sequence of A* 11:256Q was confirmed to be identical to A*11:02:01from exon 1 to exon 8 except for the residues from 409 to 417 where a segment of nine nucleotides (TACCGGCAG) is deleted in A*11:256Q. The HLA haplotype associated with A*11:256Q was deduced as A*11:256Q-B*27-DRB1*12. In exons 2 and 3, the DNA sequence of A*02:621 is identical to A*02:01:01:01 except at residue 169 where T of A*02:01:01:01 is replaced by C in A*02:621 (at codon 33; TTC->CTC). The HLA haplotype in association with A*02:621 was deduced as A*02:621-B*15:18-DRB1*12:02. Conclusion: The information on the ethnicity of the A*11:256Q and A*02:621 alleles and the deduced probable HLA haplotypes associated with the two low-incidence alleles reported here are valuable to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid in finding compatible donors in unrelated bone marrow donor registries when a patient carries these uncommon HLA alleles.