ABSTRACT
BACKGROUND: Autologous stem cell transplantation is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell collection. STUDY DESIGN AND METHODS: This was a retrospective study with data from transplantation candidates between September 2015 and December 2021 being analyzed. The medical record of each patient was reviewed to mine mobilization information. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood cell count. The primary outcome, good mobilization, was defined as a CD34+ cell count ≥20/µL. RESULTS: This study included 807 patients. Increased patient weight, low mean corpuscular volume, high nucleated red blood cells, peripheral blood mononuclear cell and immature granulocyte counts were significantly associated with good mobilization. In addition, patients diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma. The model was applied to a validation set to identify patients who underwent apheresis (CD34+ cell count ≥10 µL), resulting in a sensitivity of 69 %, a specificity of 95 %, positive predictive value of 98 %, and a negative predictive value of 50 %. CONCLUSION: Success in mobilization was greater in patients who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher body weight, and nucleated red blood cells, immature granulocytes and mononuclear cell counts, as well as low mean corpuscular volumes, were associated with successful mobilization.
ABSTRACT
OBJECTIVE: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation is a widely applied treatment for hematological and autoimmune diseases. Little is known about the effects of this therapy on multipotent mesenchymal stromal cells (MSCs). We aimed to characterize, morphologically and functionally, MSCs isolated from bone marrow aspirates of patients after HDCT. MATERIALS AND METHODS: We studied 12 consecutive lymphoma patients submitted to BEAM conditioning regimen followed by autologous stem cell transplantation 28 to 1836 days before the sample collection. Thirteen normal donors were used as control. MSCs were isolated by adherence to plastic and expanded ex vivo by culture in flasks containing alpha-minimum essential medium plus 15% fetal bovine serum. RESULTS: The cell population isolated showed a typical MSC morphology, immunophenotype, and differentiation capacity into adipogenic, osteogenic, and chondrogenic lineages. The MSCs obtained from patients with Hodgkin's disease and non-Hodgkin's lymphoma showed decreased fibroblastoid colony-forming unit count (p = 0.023) and increased doubling time (p = 0.031) related to the control group. The total cell expansion of MSCs from normal subjects was marginally superior to the patient group (p = 0.064). There were no differences in gene expression profile, MSCs plasticity, or hematopoiesis support capability between control and patient group. CONCLUSIONS: Results suggest that HDCT applied to lymphoma patients damaged MSCs, which was demonstrated by their reduced clonogenic potential, doubling time, and cell expansion rates when compared to controls.
Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols , Bone Marrow Cells/drug effects , Hodgkin Disease , Lymphoma, Non-Hodgkin , Mesenchymal Stem Cells/drug effects , Adult , Cells, Cultured , Female , Flow Cytometry , Humans , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Young AdultABSTRACT
O transplante autólogo de células-progenitoras hematopoéticas (CPH) requer, na maioriadas vezes, a sua criopreservação a fim de manter sua viabilidade até o momento da infusão, que pode se dar meses ou anos depois da coleta. A criopreservação adequada das CPHs é feita ao submeter a suspensão celular a velocidades lentas de congelamento (1 a 3ºC/minuto), e com o emprego de substâncias chamadas crioprotetoras, sendo a mais usada o dimetilsulfóxido (Me2SO4), um agente coligativo que diminui o conteúdo de água livre tanto no espaço intra como no extracelular. Portanto, este composto diminui o tamanho e o número dos cristais de gelo. O descongelamento das CPHs é feito rapidamente. A suspensão celular pode então ser infundida sem posterior manipulação ou ser submetida a lavagem para remover o Me2SO4, restos celulares e hemoglobina livre, potencialmente tóxicos tanto para o paciente quanto para as células.
Autologous transplantation of hematopoietic progenitor cells requires most of the times the cryopreservation of the hematopoietic progenitor cells (HPC) to maintain their viability until the infusion, which can occur months to years after their collection. Adequate cryopreservation of HPC is realized by submitting the cells to slow freezing velocity (1-3°C/minute) and by employing cryoprotectant agents like the dimethylsulphoxide (Me2SO4), the most used, a colligative agent that reduces the free water content into the cellules and in the extracellular medium. As a consequence, this compound reduces the size and number of ice. The thawing of HPC is done rapidly. The cell suspension can then be infused un manipulated or washed to remove Me2SO4, cellular debris and free hemoglobin, potentially toxic both to patients and to cells.
