Unraveling stem cell and progenitor subsets in autologous grafts according to methods of mobilization: implications for prediction of hematopoietic recovery.

BACKGROUND AIMS: In the autologous setting, granulocyte colony-stimulating factor (G-CSF) (G), or, when failing, G plus plerixafor (G+P), are common regimens for mobilization of stem cells into peripheral blood. To delineate mobilization effects on graft composition and hematopoietic recovery, we compared contents of stem cells and progenitor cells in products of G+P- and G patients. Paired samples of G+P patients and prior insufficient G mobilization were available for analyses. METHODS: Subset analyses of grafts were performed by flow cytometry and myeloid colony-forming assay. In search of new markers to ascertain graft quality, we determined the fractions of aldehyde dehydrogenase bright (ALDH(br)) cells. RESULTS: G grafts contained higher percentages of CD34+ cells, CD34+CD38- cells, and committed progenitors (CD34+CD38+) compared with G+P grafts. A detailed characterization of the mobilized CD34+ cell subset showed higher percentages of CD38- among the CD34+ cells of the G+P group (P = 0.032). In contrast, the CD34+ cell subset in G grafts was characterized by a higher percentage of ALDH(br) cells (P < 0.0001). Studying engraftment and day +100 graft function the G and G+P transplanted patients were comparable with respect to neutrophils, whereas in platelets they differed. In the prediction of engraftment and hematopoietic recovery, the dose of infused ALDH(br) cells correlated best to both platelet (r = 0.565, P = 0.002) and neutrophil reconstitution (r = 0.366, P = 0.06). CONCLUSIONS: Besides showing dissimilar distributions of CD34+CD38- cells and progenitors in G and G+P grafts, this study further designated ALDH(br) as a promising marker in determination and prediction of graft quality and hematopoietic recovery.

Very long-term remission induced by short-term rituximab monotherapy in a patient with heavily pretreated, chronic immune thrombocytopenic purpura.

The management of patients with refractory immune thrombocytopenic purpura (ITP) may be difficult. We describe a rapid-onset very long-term remission (9 years) induced by short-term rituximab monotherapy in a 62-year-old man with treatment-refractory chronic ITP. Over a 30-year period from the original diagnosis to last follow-up, the patient needed renewed treatment twelve times within the first two decades and was subsequently brought in continuous complete remission for the last decade by a single course of rituximab. The effect of rituximab in ITP has previously been described. However, in chronic, treatment-refractory ITP occurring in elderly patients, remission rates tend to be low and of short duration.

Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).