Is split-dose better than single-dose? Results of Turkish Stem Cell Coordination Center (TURKOK) donors in the era of rising biosimilar G-CSF.

BACKGROUND: Turkish Stem Cell Coordination Center (TURKOK) carries out the procurement process of unrelated allogeneic hematopoietic stem cells in Turkey. This study aims to compare the efficacy of both once-daily and divided-dose G-CSF administration and the original and biosimilar G-CSF use and the frequency and severity of adverse events in TURKOK donors. METHOD: The study was conducted retrospectively with 142 healthy TURKOK donors. For PBSC mobilization, two different subcutaneous G-CSF programs were used as 10 µ/kg/day single-dose and 5 µ/kg/12 h. Neupogen (Amgen, Puerto Rico) and Tevagrastim (Teva, Kfar Saba, Israel) were used as G-CSF. All donors started apheresis on the fifth day, and all side effects were recorded during the procedure. RESULTS: Stem cell yield was similar between single-dose and divided-doses based on donor weight, favoring the split-dose based on recipient weight (P = .506 and P = .023, respectively). Both G-CSF posologies were comparable if the target CD34+ cell yield was ≥4 × 106 /kg. CD34+ cell yield was equivalent when evaluated against recipient weight, significantly favoring Tevagrastim vs Neupogen by donor weight (P = .740 and P = .021, respectively). Side effects, duration of pain, and need for analgesia favor Tevagratim over Neupogen. CONCLUSION: Split-dose may be recommended for cases where the need for large numbers of CD34+ cells to be harvested is anticipated due to significant cell yield relative to recipient weight. However, sufficient hematopoietic stem cells can be collected with both posology. Tevagrastim is non-inferiority effective to Neupogen. Side effects during administration are both low-grade and temporary.

Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors.

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 µg/kg for lenograstim, 9.8 µg/kg for biosimilar filgrastim, and 9.3 µg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF.

A dispermic chimerism detected in a Taiwanese potential unrelated hematopoietic stem cell donor.

Chimerism is defined as the presence of 2 or more than 1 genetically distinct cell populations in an organism. Dispermic chimeras are derived from the fertilization of 1 or 2 matured nuclei by 2 sperms. We here report detection of a healthy and phenotypically normal female with normal ABO red blood cell typing in whom dispermic chimerism was suspected after 3 alleles were identified at multiple human leukocyte antigen (HLA) loci using molecular HLA analysis. Molecular HLA typing showed the donor to have 3 HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles in blood, saliva and nail samples. In addition, 3 of her 9 short tandem repeat loci also showed to have 3 distinct alleles in blood, nail and saliva specimens. In all investigations, the third alleles were attributed to a dual paternal contribution. This case represents a dispermic chimerism, with 2 paternal and 1 maternal haplotypes variably distributed throughout body tissues in a healthy and phenotypically normal female without abnormalities in erythrocyte ABO blood group. The origin of this chimerism is probably due to the fertilization of a single egg and its polar body, or a parthenogenetic egg, by 2 sperms.

HLA-A*33:03:31, a novel variant of HLA-A*33:03, discovered in a Taiwanese individual.

One nucleotide substitution of HLA-A*33:03:01 results in a novel allele, HLA-A*33:03:31.