Unresolved issues in allogeneic hematopoietic cell transplantation for non-malignant diseases

Abstract

Allogeneic hematopoietic cell transplantation (HCT) can be curative for a variety of non-malignant diseases (NMDs) as well as hematological malignancies. However, there are several fundamental differences between HCT for NMDs and hematological malignancies, which may necessitate the use of alternative HCT strategies. For example, these diseases differ in the intensity of conditioning regimen sufficient to improve disease. In addition, patients with NMDs are at higher risk of graft failure or mixed chimerism following HCT, and gain no or little survival benefit from graft-versus-host disease. Because more than 80% of patients with NMDs become long-term survivors, greater attention has been paid to late adverse effects and decreased of quality of life after HCT. This review addresses several unresolved issues in allogeneic HCT for patients with NMDs, such as (1) stem cell source, (2) conditioning regimen, (3) use of serotherapy or low-dose irradiation, and (4) therapeutic intervention for mixed chimerism. Resolving these issues may improve transplant outcomes in patients with NMDs.

A novel flow-cytometric based method to assess post-HSCT donor chimerism exploiting RNA hybridization

“…As a proof of principle, we exploited sex mismatch, as routinely done also for standard STR-PCR, which allows direct application of the method to a high percentage of patients independently from the degree of mismatch between donor and recipient, differently from previously reported flow cytometric methods [ 15 ]. So far, chimerism analysis on specific subsets has been shown to have important prognostic implications [ 3 , 4 ]. Indeed, the main advantage of this platform is that it allows direct analysis of chimerism at single-cell resolution in specific hematopoietic subsets avoiding prior FACS sorting dramatically, thus abating the costs of such analysis (around 10-fold less).…”

“…From a technical standpoint, the gold standard is to assess chimerism by PCR technique, in particular short tandem repeat PCR (STR-PCR), a technique which however allows only limited sensitivity (1–5%) [ 1 , 2 ]. In non-malignant diseases, such as sickle cell disease (SCD) or thalassemia, mixed chimerism is often observed since the development of reduced intensity conditioning regimens [ 3 , 4 ]. In this context, a degree of disease-specific donor chimerism can still be sufficient to relieve the clinical phenotype but deserves close follow-up and specific therapeutic interventions.…”

Endocrine complications after hematopoietic stem cell transplantation during childhood—Results from a close follow‐up in a cohort of 152 patients

“…21,22 Most patients with nonmalignant conditions do not receive conventional chemotherapy and RT (higher doses than TBI) before HSCT. 21 These factors may contribute to differences between the two groups in the development of certain endocrinopathies, such as thyroid dysfunction or hypogonadism. Moreover, endocrine complications such as thyroid carcinoma may show some genetic predisposition, but we were not able to retrieve data regarding familial history.…”

“…Although comparable, there may be some differences between their treatment. In HSCT for nonmalignant conditions, reduced‐intensity conditioning regimens are used preferentially, such as lower doses of alkylating agents or TBI 21,22 . Most patients with nonmalignant conditions do not receive conventional chemotherapy and RT (higher doses than TBI) before HSCT 21 .…”

“…In HSCT for nonmalignant conditions, reduced-intensity conditioning regimens are used preferentially, such as lower doses of alkylating agents or TBI. 21,22 Most patients with nonmalignant conditions do not receive conventional chemotherapy and RT (higher doses than TBI) before HSCT. 21 These factors may contribute to differences between the two groups in the development of certain endocrinopathies, such as thyroid dysfunction or hypogonadism.…”