Contributions
Abstract: PB2125
Type: Publication Only
Background
High-dose chemotherapy and subsequent Autologous hematopoietic stem cell transplantation (AutoHSCT) are widely used at the stage of remission consolidation in patients with multiple myeloma (MM). AutoHSCT is not equally effective for all patients. The ineffective AutoHSCT group includes patients undergone unsuccessful mobilization and ones with early relapse after AutoHSCT. AutoHSCT success depends on many factors, including the patient's age, general status and the status of comorbidity, the intensity and duration of prior therapy, etc. No less important is the state of the niche of HSC, which has been subjected to toxic effects of aggressive treatment, as well as the success of homing and fixing poured HSC in niches, which is largely determined by the morphological and functional characteristics of the main stromal components of the niche.
Aims
To investigate the morphological and functional characteristics of the main stromal components of the niche HSC in patients with multiple myeloma and inefficient AutoHSCT.
Methods
12 trepanobiopsy of bone marrow from patients diagnosed with progressive MM (5 men and 7 women) were used in the study. The age of the patients ranged from 52 to 68 (median 57 years). Inefficient mobilization of HSC was noted for 7 patients and early relapse (i.e. within 12 months after AutoHSCT) for five. The study applied histological, immunohistochemical (IHC) and morphometric methods (VideoTest®).
Results
Assessment of the amount of infiltration of the bone marrow plasma cells is one of the main criteria for diagnosis of MM. Histological examination of trepanobiopsies of patients with MM showed non-uniform cellular infiltration of myeloma cells in the bone marrow. All types of bone marrow infiltration were identified in the group studied: focal (2 cases), interstitial 5-10% lesions (4 cases), interstitial 20-30% lesions (4 cases), diffuse (2 cases). Bone marrow damage did not exceed 10% for half of the cases (6 patients). We carried out a histomorphometric analysis of niche-forming structures of bone marrow microenvironment: vessels, endosteal cells, proteins of extracellular and intratrabecular matrix (collagen I, III, IV). Following trends were revealed during analysis. An increase of microcirculation vessels number especially in 8 patients It comprises 15.2 ± 2.8% and 9.1±1.2% for experimental and control (bone marrow donors) respectively(p<0.05). A marked increase in cell per unit length of bone trabecular was observed for endost of 2.7±0.5 compared with 1.4±0.2 in the control (p<0.05). Pronounced expression of CD56 tumor cells in subendosteal area was revealed in case of damage to the bone marrow exceeded 30%. Osteolysis was observed by the type of smooth resorption. Increased expression of collagen type IV was observed around all blood vessels of microcirculation, venules, arterioles. A typical feature was the appearance of focal network of reticulin fiber in subendosteal and perivascular spaces. Despite the treatment, microenvironment of the bone marrow retained the features of the tumor-associated environment.
Conclusion
Discovered key features of stromal elements of the bone marrow niche HSC evidence of serious violation of their morphological status, which is directly reflected in the results AutoHSCT. Studies of the stromal component of bone marrow can give clinicians additional information for successful training of patients with MM to AutoHSCT.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Hematopoietic cell transplantation, Hematopoietic microenvironment, Hematopoietic Stem Cell, Multiple Myeloma
Abstract: PB2125
Type: Publication Only
Background
High-dose chemotherapy and subsequent Autologous hematopoietic stem cell transplantation (AutoHSCT) are widely used at the stage of remission consolidation in patients with multiple myeloma (MM). AutoHSCT is not equally effective for all patients. The ineffective AutoHSCT group includes patients undergone unsuccessful mobilization and ones with early relapse after AutoHSCT. AutoHSCT success depends on many factors, including the patient's age, general status and the status of comorbidity, the intensity and duration of prior therapy, etc. No less important is the state of the niche of HSC, which has been subjected to toxic effects of aggressive treatment, as well as the success of homing and fixing poured HSC in niches, which is largely determined by the morphological and functional characteristics of the main stromal components of the niche.
Aims
To investigate the morphological and functional characteristics of the main stromal components of the niche HSC in patients with multiple myeloma and inefficient AutoHSCT.
Methods
12 trepanobiopsy of bone marrow from patients diagnosed with progressive MM (5 men and 7 women) were used in the study. The age of the patients ranged from 52 to 68 (median 57 years). Inefficient mobilization of HSC was noted for 7 patients and early relapse (i.e. within 12 months after AutoHSCT) for five. The study applied histological, immunohistochemical (IHC) and morphometric methods (VideoTest®).
Results
Assessment of the amount of infiltration of the bone marrow plasma cells is one of the main criteria for diagnosis of MM. Histological examination of trepanobiopsies of patients with MM showed non-uniform cellular infiltration of myeloma cells in the bone marrow. All types of bone marrow infiltration were identified in the group studied: focal (2 cases), interstitial 5-10% lesions (4 cases), interstitial 20-30% lesions (4 cases), diffuse (2 cases). Bone marrow damage did not exceed 10% for half of the cases (6 patients). We carried out a histomorphometric analysis of niche-forming structures of bone marrow microenvironment: vessels, endosteal cells, proteins of extracellular and intratrabecular matrix (collagen I, III, IV). Following trends were revealed during analysis. An increase of microcirculation vessels number especially in 8 patients It comprises 15.2 ± 2.8% and 9.1±1.2% for experimental and control (bone marrow donors) respectively(p<0.05). A marked increase in cell per unit length of bone trabecular was observed for endost of 2.7±0.5 compared with 1.4±0.2 in the control (p<0.05). Pronounced expression of CD56 tumor cells in subendosteal area was revealed in case of damage to the bone marrow exceeded 30%. Osteolysis was observed by the type of smooth resorption. Increased expression of collagen type IV was observed around all blood vessels of microcirculation, venules, arterioles. A typical feature was the appearance of focal network of reticulin fiber in subendosteal and perivascular spaces. Despite the treatment, microenvironment of the bone marrow retained the features of the tumor-associated environment.
Conclusion
Discovered key features of stromal elements of the bone marrow niche HSC evidence of serious violation of their morphological status, which is directly reflected in the results AutoHSCT. Studies of the stromal component of bone marrow can give clinicians additional information for successful training of patients with MM to AutoHSCT.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Hematopoietic cell transplantation, Hematopoietic microenvironment, Hematopoietic Stem Cell, Multiple Myeloma