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Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gonzalez-Montes, Osca-Gelis, Rodriguez-Romanos, Villavicencio, González-Bártulos, Llopis, Clapes, Oriol, Sureda, Escoda, Sarrà, Garzó, Lloveras, Gómez, Granada and Gallardo.)

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonzalez-Montes, Rodriguez-Romanos, Villavicencio, Osca-Gelis, González-Bártulos, Llopis, Clapes, Oriol, Sureda, Escoda, Sarrà, Garzó, Lloveras, Díez, Granada and Gallardo.)

Background Aims: Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization., Methods: Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 10(6) CD34(+)cells/kg body weight (BW)., Results: The median age was 53 years (range 4-70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkin's lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkin's lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte-colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34(+)cell count in PB > 13.8/μL was enough to ensure ≥ 2 × 10(6) CD34(+)cells/kg, with high sensitivity (90%) and specificity (91%)., Conclusions: The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34(+) cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.

Background aims. Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization. Methods. Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 106 CD34+cells/kg body weight (BW). Results. The median age was 53 years (range 4-70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkin's lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkin's lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte-colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34+cell count in PB > 13.8/μL was enough to ensure ≥ 2 × 106 CD34+cells/kg, with high sensitivity (90%) and specificity (91%). Conclusions. The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34+ cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization. [ABSTRACT FROM AUTHOR]

Patients with hematological malignancies who relapse after autologous stem cell transplantation (auto-SCT) generally have poor prognosis. Salvage treatment is often associated with severe toxicities. The aim of our study was to evaluate retrospectively the toxicity and outcome of rescue therapy in patients with acute leukemias, non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and multiple myeloma (MM) relapsing after auto-SCT. Fifty-four of the 62 patients who relapsed received some form of salvage chemotherapy. Six (10%) patients were treated by second stem cell transplantation, which was allogeneic in 5 cases. Toxicity of the salvage therapy was significant. As a result of adverse effects, salvage therapy had to be discontinued or reduced in 14 patients (26%). The outcome of salvage was evaluated after 90 days. Of the treated patients, 14 (26%) entered into complete remission with another 5 (9%) reaching partial response. The disease was stabilized in 5 patients (9%) but 30 (56%) patients were in progression or dead. Overall survival of the patients was poor with the median survival of 8.7 months after relapse and the leading cause of death being progressive disease. In conclusion, the development of new, more efficient regimens is critical if disease-free survival is to be increased in patients who relapse after auto SCT. [ABSTRACT FROM AUTHOR]