Vadim Baykov - Academia.edu (original) (raw)

Papers by Vadim Baykov

Cellular Therapy and Transplantation

Transplantation and Cellular Therapy, 2021

BACKGROUND The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy ... more BACKGROUND The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10-15% of patients are cured by the procedure. Preclinical studies indicate that substitution of posttransplantation cyclophosphomide (PTCY) with bendamustine (PTB) in a prophylaxis regimen may be associated with augmented graft-versus-leukemia (GVL) reaction. OBJECTIVE establish the optimal dose of PTB and evaluate the anti-leukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. STUDY DESIGN In the prospective trial (NCT02799147) PTB was administered in doses 140, 100 and 70 mg/m2 on days +3,+4. Myeloablative conditioning with fludarabine and oral busulfan was performed in all patients. First 12 patients received single-agent PTB and subsequent- combination with tacrolimus and MMF. Inclusion criteria were acute myeloblstic (AML) or lymphoblstic leukemia (ALL) refractory to at least on induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. Seven patients were enrolled in the 140 mg/m2 cohort (due to stopping rule), 10 in 100 mg/m2 and 10 in 70 mg/m2 group, including 22 with AML and 5 with ALL. Primary refractory disease was documented in 41% of patients and secondary refractory - in 59%. Median blast count in the bone marrow at the start of the conditioning was 18% (range 6-97%). Matched sibling transplantation was performed in 5 patients, matched or mismatched unrelated in 15, and haploidentical in 7. RESULTS Engraftment was documented in 93% of patients, including 89% with complete remission (CR) and 63% without measurable residual disease (MRD). After PTB prophylaxis we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3-5 in 44% of patients. Most often clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation (DIC) in 37%, CNS toxicity in 26%. Development of CRS was associated with HLA-mismatched donor (75% vs 20%, p= 0.0043). Classical acute GVHD was documented in 44% of patients. Grade II-IV acute GVHD was associated with grade 3-5 CRS (67% vs 25%, p=0.031). Moderate and severe chronic GVHD in the 100-day survivors was more often observed after single-agent PTB than after the combination immunosuppression (100% vs 18%, p=0.002). Relatively low relapse incidence was observed for this patient population. Three-year overall survival was 28% (95% CI 13-46%), event-free-survival 29% (95% CI 13-46%). NRM was 46% (95% CI 25-64%), CIR was 26% (95%CI 11-44). No relapses were documented after day+100. There was no statistical differences between the dose groups (p=0.3481), however the survival was higher in the 100 mg/kg group. The survival was higher in AML than ALL (35% vs 0%, p=0.0157). CONCLUSION PTB represents a promising option to augment GVL effect in refractory AML, however high CRS-associated mortality requires additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation.

Human myeloma cells adhere to fibronectin in response to hepatocyte growth factor Multiple myelom... more Human myeloma cells adhere to fibronectin in response to hepatocyte growth factor Multiple myeloma (MM) cells areusually found in one particularlocation, the bone marrow (BM). This tropism can be explained if factors present only in the BM are absolutely crit-ical for the survival and growth of MM cells. Such factors can be cell adhesion sites in the bone extracellular matrix or cytokines secreted by cells in the marrow microenvironment. Adhesion between MM cells and the microenvironment might be beneficial to MM cells in several ways. For instance, adhesion is reported to induce the secretion of myeloma growth factors, such as interleukin-6 (IL-6)1 and

Blood, 2020

Background.Tumor tissue in classical Hodgkin Lymphoma (cHL) contains 1-10% malignant Hodgkin/Reed... more Background.Tumor tissue in classical Hodgkin Lymphoma (cHL) contains 1-10% malignant Hodgkin/Reed-Sternberg cells and a significant number of immune cells in the tumor microenvironment that are characterized by expression of inhibitory molecules (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT). Despite overall effectiveness of anti-PD-1 treatment many patients still have relapsed or refractory (r/r) disease, therefore the search for predictive/prognostic biomarkers in patients on immunotherapy is highly demanded. Materials and methods.The study included 39 primary tumor specimens from patients with r/r cHL obtained before starting the treatment with nivolumab (primary biopsies). Specimens from 11 patients were studied before and after treatment (sequential biopsies). Treatment response was evaluated by PET-CT according to LYRIC criteria. Immunohistochemical staining for CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT was performed with an automated staining system (Bond III; Leica Biosystems). Th...

Pediatric Hematology/Oncology and Immunopathology, 2021

Lymphoblastic lymphoma (LBL) in children is curable in most cases, but there is still a significa... more Lymphoblastic lymphoma (LBL) in children is curable in most cases, but there is still a significant proportion of patients in whom standard therapy is ineffective. Thus, patients develop a relapse or a primary refractory disease in about 10% of cases (R/R). In this case, the main treatment method is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The choice in favor of transplantation is predominantly based on the experience in adult patients. A small number of pediatric patients accounts for the limited data in pediatrics. The prognosis of these patients is always extremely poor. It has been shown that the survival of patients after allo-HSCT is higher only if remission is achieved prior to the transplantation. In order to provide more evidence in support of allo-HSCT, randomized clinical trials are needed. However, such studies in the field of allo-HSCT are quite difficult to conduct, and this necessitates the search for alternative methods of evidence-based medici...

Pediatric Hematology/Oncology and Immunopathology, 2021

There is no doubt that autologous hematopoietic stem cell transplantation (auto-HSCT) with high-d... more There is no doubt that autologous hematopoietic stem cell transplantation (auto-HSCT) with high-dose polychemotherapy (PCT) is a standard method for the second remission consolidation in case of relapse or for the fist remission consolidation in refractory disease in adult patients with non-Hodgkin lymphomas (NHL) (with the exception of lymphoblastic lymphoma in which allogeneic transplantation is preferable). Similar to patients older than 18 years of age, an identical algorithm is applied in pediatric patients, however in the absence of randomized clinical trials and due to a small number of patients, the evidence base in children is weaker compared to adults, which complicates the analysis. Due to a signifiant number of nonrandomized studies confiming the benefis of transplantation, it is impossible to plan and make a direct comparison of auto-HSCT and standard chemotherapy in pediatric patients within a randomized study primarily because of ethical reasons. Although transplantat...

Olesya G. Smykova, Kirill V. Lepik, Natalia B. Mikhailova, Elena V. Kondakova, Evgenia S. Borzenk... more Olesya G. Smykova, Kirill V. Lepik, Natalia B. Mikhailova, Elena V. Kondakova, Evgenia S. Borzenkova, Elena E. Lepik, Yuri R. Zalyalov, Lilia V. Stelmakh, Vadim V. Baykov, Ivan S. Moiseev, Alexander D. Kulagin, Boris V. Afanasyev RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia Nivolumab-based immunotherapy in relapsed/refractory B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma Cellular Therapy and Transplantation (CTT). Vol. 10, No. 1, 2021 doi: 10.18620/ctt-1866-8836-2021-10-1-37-43 Submitted: 08 March 2021, accepted: 09 April 2021

Blood, 2020

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory ... more Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease prog...

Blood, 2020

Background Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associa... more Background Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associated with HIV. Despite improved understanding of this disease, its prognosis remains poor with short overall survival. There is no standard of care for this entity. Recent advances in the treatment of HIV-associated and aggressive lymphomas have not yet significantly improved the outcomes of patients with PbL. Methods We investigate epidemiological characteristics and the results of the treatment of the HIV-related PbL in large cohort of HIV-related lymphoma patients for a 7-year period (2014-2020). During the observation period, 22 cases of HIV-related PbL were registered in three centers and selected for the analysis from the national multicenter retrospective study database. The median follow-up was 17,8 (4-57,4) months. Results The PbL accounted for 8,9% of lymphomas in HIV-infected patients (22/247). The median age was 42 years (32-61), males - 9 (41%). Most of the patients (n=19, 86...

Cancers, 2021

To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgk... more To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13–63) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells p = 0.0086; for CD68-positive cells p = 0.037), while a low n...

Blood, 2021

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3... more ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic inv...

Leukemia Research Reports, 2020

In our single-center retrospective study we evaluated whether level of different checkpoint molec... more In our single-center retrospective study we evaluated whether level of different checkpoint molecules in bone marrow biopsies at diagnosis affect the clinical course of patients with myelodysplastic syndrome (MDS). Methods and results: A consecutive cohort of 55 MDS patients treated in our center from 2003 to 2018 with available bone marrow biopsies at time of diagnosis was studied. We used a technique able to detect the expression of the following antigens: PD-1, PD-L1, PD-L2, LAG-3, Gal-9, TIM-3, CD80. The association between expression level and 3-year overall and relapse-free survival and time-to-progression was analyzed. Intensive expression of TIM-3 was observed in 100% of cases. Also, in most cases, moderate Gal-9 expression was observed. With 3-year follow-up disease progression was seen in 72.9% of patients with high CD80 level and 52.1% of patients with low CD80 level (p=0.04). PD-1, CTLA4 and TIM-3 ligands were co-expressed in the majority of patients. General checkpoint ligand expression level also was associated with increased 3-year incidence of progression: 67.2% of patients with high level of checkpoint ligands progressed, while in the group with low checkpoint ligand expression level progression was observed only in 33.3% of cases (p=0.059). There was an association between the expression of checkpoint molecules CD80, PD-L2, TIM3, the number of bone marrow blasts and risk according to IPSS and IPSS-R scales. Conclusions: Our preliminary study underlined heterogeneous immune checkpoint molecules expression in MDS and warrants further studies to define the role of this heterogeneity and develop optimal treatment approaches.

Cellular Therapy and Transplantation

Transplantation and Cellular Therapy, 2021

BACKGROUND The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy ... more BACKGROUND The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10-15% of patients are cured by the procedure. Preclinical studies indicate that substitution of posttransplantation cyclophosphomide (PTCY) with bendamustine (PTB) in a prophylaxis regimen may be associated with augmented graft-versus-leukemia (GVL) reaction. OBJECTIVE establish the optimal dose of PTB and evaluate the anti-leukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. STUDY DESIGN In the prospective trial (NCT02799147) PTB was administered in doses 140, 100 and 70 mg/m2 on days +3,+4. Myeloablative conditioning with fludarabine and oral busulfan was performed in all patients. First 12 patients received single-agent PTB and subsequent- combination with tacrolimus and MMF. Inclusion criteria were acute myeloblstic (AML) or lymphoblstic leukemia (ALL) refractory to at least on induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. Seven patients were enrolled in the 140 mg/m2 cohort (due to stopping rule), 10 in 100 mg/m2 and 10 in 70 mg/m2 group, including 22 with AML and 5 with ALL. Primary refractory disease was documented in 41% of patients and secondary refractory - in 59%. Median blast count in the bone marrow at the start of the conditioning was 18% (range 6-97%). Matched sibling transplantation was performed in 5 patients, matched or mismatched unrelated in 15, and haploidentical in 7. RESULTS Engraftment was documented in 93% of patients, including 89% with complete remission (CR) and 63% without measurable residual disease (MRD). After PTB prophylaxis we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3-5 in 44% of patients. Most often clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation (DIC) in 37%, CNS toxicity in 26%. Development of CRS was associated with HLA-mismatched donor (75% vs 20%, p= 0.0043). Classical acute GVHD was documented in 44% of patients. Grade II-IV acute GVHD was associated with grade 3-5 CRS (67% vs 25%, p=0.031). Moderate and severe chronic GVHD in the 100-day survivors was more often observed after single-agent PTB than after the combination immunosuppression (100% vs 18%, p=0.002). Relatively low relapse incidence was observed for this patient population. Three-year overall survival was 28% (95% CI 13-46%), event-free-survival 29% (95% CI 13-46%). NRM was 46% (95% CI 25-64%), CIR was 26% (95%CI 11-44). No relapses were documented after day+100. There was no statistical differences between the dose groups (p=0.3481), however the survival was higher in the 100 mg/kg group. The survival was higher in AML than ALL (35% vs 0%, p=0.0157). CONCLUSION PTB represents a promising option to augment GVL effect in refractory AML, however high CRS-associated mortality requires additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation.

Human myeloma cells adhere to fibronectin in response to hepatocyte growth factor Multiple myelom... more Human myeloma cells adhere to fibronectin in response to hepatocyte growth factor Multiple myeloma (MM) cells areusually found in one particularlocation, the bone marrow (BM). This tropism can be explained if factors present only in the BM are absolutely crit-ical for the survival and growth of MM cells. Such factors can be cell adhesion sites in the bone extracellular matrix or cytokines secreted by cells in the marrow microenvironment. Adhesion between MM cells and the microenvironment might be beneficial to MM cells in several ways. For instance, adhesion is reported to induce the secretion of myeloma growth factors, such as interleukin-6 (IL-6)1 and

Blood, 2020

Background.Tumor tissue in classical Hodgkin Lymphoma (cHL) contains 1-10% malignant Hodgkin/Reed... more Background.Tumor tissue in classical Hodgkin Lymphoma (cHL) contains 1-10% malignant Hodgkin/Reed-Sternberg cells and a significant number of immune cells in the tumor microenvironment that are characterized by expression of inhibitory molecules (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT). Despite overall effectiveness of anti-PD-1 treatment many patients still have relapsed or refractory (r/r) disease, therefore the search for predictive/prognostic biomarkers in patients on immunotherapy is highly demanded. Materials and methods.The study included 39 primary tumor specimens from patients with r/r cHL obtained before starting the treatment with nivolumab (primary biopsies). Specimens from 11 patients were studied before and after treatment (sequential biopsies). Treatment response was evaluated by PET-CT according to LYRIC criteria. Immunohistochemical staining for CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT was performed with an automated staining system (Bond III; Leica Biosystems). Th...

Pediatric Hematology/Oncology and Immunopathology, 2021

Lymphoblastic lymphoma (LBL) in children is curable in most cases, but there is still a significa... more Lymphoblastic lymphoma (LBL) in children is curable in most cases, but there is still a significant proportion of patients in whom standard therapy is ineffective. Thus, patients develop a relapse or a primary refractory disease in about 10% of cases (R/R). In this case, the main treatment method is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The choice in favor of transplantation is predominantly based on the experience in adult patients. A small number of pediatric patients accounts for the limited data in pediatrics. The prognosis of these patients is always extremely poor. It has been shown that the survival of patients after allo-HSCT is higher only if remission is achieved prior to the transplantation. In order to provide more evidence in support of allo-HSCT, randomized clinical trials are needed. However, such studies in the field of allo-HSCT are quite difficult to conduct, and this necessitates the search for alternative methods of evidence-based medici...

Pediatric Hematology/Oncology and Immunopathology, 2021

There is no doubt that autologous hematopoietic stem cell transplantation (auto-HSCT) with high-d... more There is no doubt that autologous hematopoietic stem cell transplantation (auto-HSCT) with high-dose polychemotherapy (PCT) is a standard method for the second remission consolidation in case of relapse or for the fist remission consolidation in refractory disease in adult patients with non-Hodgkin lymphomas (NHL) (with the exception of lymphoblastic lymphoma in which allogeneic transplantation is preferable). Similar to patients older than 18 years of age, an identical algorithm is applied in pediatric patients, however in the absence of randomized clinical trials and due to a small number of patients, the evidence base in children is weaker compared to adults, which complicates the analysis. Due to a signifiant number of nonrandomized studies confiming the benefis of transplantation, it is impossible to plan and make a direct comparison of auto-HSCT and standard chemotherapy in pediatric patients within a randomized study primarily because of ethical reasons. Although transplantat...

Olesya G. Smykova, Kirill V. Lepik, Natalia B. Mikhailova, Elena V. Kondakova, Evgenia S. Borzenk... more Olesya G. Smykova, Kirill V. Lepik, Natalia B. Mikhailova, Elena V. Kondakova, Evgenia S. Borzenkova, Elena E. Lepik, Yuri R. Zalyalov, Lilia V. Stelmakh, Vadim V. Baykov, Ivan S. Moiseev, Alexander D. Kulagin, Boris V. Afanasyev RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia Nivolumab-based immunotherapy in relapsed/refractory B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma Cellular Therapy and Transplantation (CTT). Vol. 10, No. 1, 2021 doi: 10.18620/ctt-1866-8836-2021-10-1-37-43 Submitted: 08 March 2021, accepted: 09 April 2021

Blood, 2020

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory ... more Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease prog...

Blood, 2020

Background Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associa... more Background Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associated with HIV. Despite improved understanding of this disease, its prognosis remains poor with short overall survival. There is no standard of care for this entity. Recent advances in the treatment of HIV-associated and aggressive lymphomas have not yet significantly improved the outcomes of patients with PbL. Methods We investigate epidemiological characteristics and the results of the treatment of the HIV-related PbL in large cohort of HIV-related lymphoma patients for a 7-year period (2014-2020). During the observation period, 22 cases of HIV-related PbL were registered in three centers and selected for the analysis from the national multicenter retrospective study database. The median follow-up was 17,8 (4-57,4) months. Results The PbL accounted for 8,9% of lymphomas in HIV-infected patients (22/247). The median age was 42 years (32-61), males - 9 (41%). Most of the patients (n=19, 86...

Cancers, 2021

To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgk... more To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13–63) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells p = 0.0086; for CD68-positive cells p = 0.037), while a low n...

Blood, 2021

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3... more ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic inv...

Leukemia Research Reports, 2020

In our single-center retrospective study we evaluated whether level of different checkpoint molec... more In our single-center retrospective study we evaluated whether level of different checkpoint molecules in bone marrow biopsies at diagnosis affect the clinical course of patients with myelodysplastic syndrome (MDS). Methods and results: A consecutive cohort of 55 MDS patients treated in our center from 2003 to 2018 with available bone marrow biopsies at time of diagnosis was studied. We used a technique able to detect the expression of the following antigens: PD-1, PD-L1, PD-L2, LAG-3, Gal-9, TIM-3, CD80. The association between expression level and 3-year overall and relapse-free survival and time-to-progression was analyzed. Intensive expression of TIM-3 was observed in 100% of cases. Also, in most cases, moderate Gal-9 expression was observed. With 3-year follow-up disease progression was seen in 72.9% of patients with high CD80 level and 52.1% of patients with low CD80 level (p=0.04). PD-1, CTLA4 and TIM-3 ligands were co-expressed in the majority of patients. General checkpoint ligand expression level also was associated with increased 3-year incidence of progression: 67.2% of patients with high level of checkpoint ligands progressed, while in the group with low checkpoint ligand expression level progression was observed only in 33.3% of cases (p=0.059). There was an association between the expression of checkpoint molecules CD80, PD-L2, TIM3, the number of bone marrow blasts and risk according to IPSS and IPSS-R scales. Conclusions: Our preliminary study underlined heterogeneous immune checkpoint molecules expression in MDS and warrants further studies to define the role of this heterogeneity and develop optimal treatment approaches.