Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function

Abstract

Poor graft function is a serious complication following allogeneic hematopoietic stem cell transplantation. Infusion of CD34 +-selected stem cells without pre-conditioning has been used to correct poor graft function, but predictors of recovery are unclear. We report the outcome of 62 consecutive patients who had primary or secondary poor graft function who underwent a CD34 +selected stem cell infusion from the same donor without further conditioning. Forty-seven of 62 patients showed hematological improvement and became permanently transfusion and growth factor-independent. In multivariate analysis, parameters significantly associated with recovery were shared CMV seronegative status for recipient/donor, the absence of active infection and matched recipient/donor sex. Recovery was similar in patients with mixed and full donor chimerism. Five-year overall survival was 74.4% (95% CI 59-89) in patients demonstrating complete recovery, 16.7% (95% CI 3-46) in patients with partial recovery and 22.2% (CI 95% 5-47) in patients with no response. In patients with count recovery, those with poor graft function in 1-2 lineages had superior 5-year overall survival (93.8%, 95% CI 82-99) than those with tri-lineage failure (53%, 95% CI 34-88). New strategies including cytokine or agonist support, or second transplant need to be investigated in patients who do not recover.

Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party

“…The cumulative incidence of grades II-IV acute GVHD was 17% and chronic GVHD 26% (13). The use of a CD34+ stem cell boost in this setting has been reported by other groups (12,16). There is insufficient evidence, in our view, to suggest the routine use of either thrombopoietin agonists or mesenchymal stem cell infusions in the management of poor graft function.…”

“…This definition mandates the absence of severe acute or chronic GVHD, relapse, and either drug-or CMV reactivation-related myelosuppression. Suggested risk factors include underlying host (age)-and disease-related characteristics (higher risk with MF), the use of unrelated donors, major ABO incompatibility, prior HLA sensitisation and low CD34+ cell doses (14)(15)(16). The Hamburg group reported on the incidence and risk factors for PGF in a single centre study of 100 patients with MF who underwent RIC allo-HCT, predominantly conditioned with either busulphanor treosulphan-based regimens and in the pre-ruxolitinib era (14).…”

CD34+ selected peripheral blood Stem Cell Boost (SCB) for Poor Graft Function (PGF) or mixed chimerism in pediatric patients, after hematopoietic stem cell transplantation: Results of a retrospective multicenter study

“…This highlights that CD34+ cells might have an immunosuppressive role, and this needs to be taken into consideration, when patients with multiple infections before and after allo-HSCT are considered for SCB. 20,21 Consequently, TRM could be significantly reduced with an earlier SCB infusion before severe infections related to neutropenia developed.…”

“…The median time to death was 175 days, meaning that the highest risk was within the first 6 months even when we analyzed patients with no immunosuppression given at SCB. This highlights that CD34+ cells might have an immunosuppressive role, and this needs to be taken into consideration, when patients with multiple infections before and after allo‐HSCT are considered for SCB 20,21 . Consequently, TRM could be significantly reduced with an earlier SCB infusion before severe infections related to neutropenia developed.…”

Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

“…A recent study ( n = 62) showed that in multivariate analysis, CMV seronegative status, the absence of active infection, and matched recipient/donor gender are favorable parameters that are strongly associated with the efficacy for CD34 + -selected SCB. 71 To sum up, CD34 + -selected SCB provides an important therapeutic option with limited adverse effects for PGF following allo-SCT.…”