Feasibility of Peripheral Blood Stem Cell Collection from Heterozygoussickle Cell Trait Donors

Introduction

Allogeneic haematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for sickle cell disease (SCD) offered to patients with a fully matched sibling (MSD) or matched unrelated donor (MUD). With a MSD/MUD donor availability of below 20% a haploidentical HSCT from a family donor either with post-transplant cyclophosphamide (post-cy) or with a TCRαß/CD19 depleted graft (T-haplo) is an increasingly successful alternative for the majority of patients. In contrast to post-cy where mostly bone marrow is used, T-haploHSCT requires the generation of a G-CSF stimulated peripheral stem cell grafts. Almost uniformly haploidentical relatives of SCD patients are heterozygous carriers of SC trait. For these donors with a genetically heterozygous sickle trait, G-SCF represents a major safety concern with regard to triggering a sickle cell crisis. Therefore, the use of sickle trait donors is prohibited or not recommended in several countries, and guidelines are currently not available due to lack of evidence.

Methods

Haploidentical related donors with heterozygousSCD (group S, n=13) as well as healthy donors (group O, n=9) were stimulated with G-CSF. In all donors a similar mobilizations schedule using G-CSF was applied. All donors were applied 10µg/kg body weight (Neupogen^®or Granocyte^®) sub cutaneous daily with first apheresis on day 5 and day 6 when necessary. The amount of mobilized CD34⁺ cells were assessed after mobilization. In addition, the harvested stem cell preparations were analysed for CD34 content after apheresis and patients monitored for potential serious adverse effects (AE) during and after the apheresis.

Results

Mobilization was tolerated well with only mild and typical AE related to apheresis procedure such as citrate reactions, joint pain, ostealgia and headache, observed equally in both groups. In most of the donors (n=13/13 and 8/9), we were able to collect a sufficient amount of CD34⁺peripheral stem cells (mean of 16.3 and 8.2 x 10^6/kg in group S and O, respectively). We observed slight increases in LDH and reticulocyte counts in few donors also without significant differences between both groups. In particular, there were no severe neurologic side effects and no problems like sickle cell crisis despite mean pre-apheresis hemoglobin concentrations of 14.1 (range 11.9-17.5) g/dL in group S.

Conclusions

Collectively, these data indicate that in the absence of a MSD or MUD donor, haploidentical family donors with heterozygoussickle cell trait provide a safe and effective alternative for collection of peripheral CD34⁺stem cells for a T-haplo HSCT.