AIM:To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure.MATERIALS AND METHODS:During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed.RESULTS:The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%.CONCLUSION:Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.

Background. The development of radical therapy for multiple myeloma (MM) is still a pressing problem. This progressive disease requires repeated courses of therapy using drugs without cross-resistance. The prognosis of “double refractory” MM which is resistant to key antitumor drugs, first generation protease inhibitors and immunomodulating agents, remains poor. The median progression-free survival (PFS) and overall survival (OS) in this cohort of patients are 5 and 9 months, respectively. Aim. The aim was to assess the effectiveness and tolerability of pomalidomide in combination with low-dose of dexamethasone in “double refractory” relapsed/refractory multiple myeloma (RRMM). Materials & Methods. According to study protocol, 10 patients from Hematology Research Center and Federal Almazov North-West Medical Research Centre with RRMM were included in the period from September 2015 to July 2016. The median age was 62.5 years (range 48-76 years), and the median number of therapy lines was 4 (range 3-5). All patients had a disease progression after the administration of bortezomib, lenalidomide, and alkylating agents. In addition, 6 (60 %) of 10 patients received high-dose melphalan chemotherapy followed by auto-HSCT. The median number of therapy lines was 6 (range 4-15). Results. The overall response rate was 60 % and the minimum response (stabilization of the disease) was observed in 40 % of patients (IMWG criteria). The median PFS was 7.8 months; OS in 18 months was observed in 70 % of cases (the median not achieved). Treatment-associated grade III-IV hematologic toxicity was observed in 2 patients (5 episodes). Non-hematological adverse events of grade III-IV included acute coronary syndrome, deep vein thrombosis, neuropathic pain, and in 1 case acute delusional disorder, which required discontinuation of the therapy. The presence of initial cytopenia and renal failure before therapy with pomalidomide did not require the dosage reduction or discontinuation of treatment. Conclusion. Pomalidomide with low-dose dexamethasone demonstrated a high overall response rate an acceptable toxicity profile in patients with RRMM.

The relationship between the type of antitumor response to induction therapy in patients with multiple myeloma (MM) and/or monoclonal gammopathy of undetermined significance (MGUS) and the level of c-MYC gene expression at the moment of disease diagnosis is studied. The expression of c-MYC in bone marrow cells was evaluated by multiplex RT-PCR. The mean levels of c-MYC gene expression in CD138(+) cells of patients with MM/MGOO are higher than in donors (p = 0.011). Relationship between the depth of antitumor response and level of C-myc expression in CD138(+) cells is detected.

Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.

Aim. To determine the frequency and pattern of blood clotting disorders in patients with multiple myeloma (MM) and to evaluate the adequacy of preventive anticoagulant or antiaggregant therapy. Subjects and methods. The prospective study conducted at the Department for High-Dose Chemotherapy and Bone Marrow Transplantation, Hematology Research Center, Ministry of Health cif the Russian Federation, in March 2012 to May 2013, enrolled 25 patients (13 men and 12 women) aged 29-72 years (median age 54 years) with new-onset MM. The latter was staged using the Dune-Salmon classification: Stages I, II, and III were determined in 2, 10, and 13 patients, respectively. Seven patients were found to have renal dysfunction (which corresponded to Substage B). The hemostasis was evaluated from the results of the following tests: activated partial thromboplastin time (APTT), thrombin time (TT), Xlla-dependent fibrinolysis time, Quick prothrombin index, international normalized ratio (INR), and fibrinogen and D-dimer concentrations. The investigators used new hemostatic techniques, such as thrombin generation test, thromboelastography, as well as thrombodynamics, a novel method to determine the characteristics of spatial clot growth. Induction therapy was performed using the PAD and VCD regimens. Thromboses were prevented by using 24-hour infusion of unfractionated heparin (500 U/hr) or by administering aspirin (100 mg/day). Results. Hypercoagulability was identified in 17 (68%) patients. Eleven (44%) patients had elevated D-dimer concentrations. The level of D-dimer was statistically significantly positively correlated with the endogenous thrombin potential and the amount of beta(2)-microglobulin. The thrombodynamic technique revealed an inverse relationship between the level of paraprotein and the optimal density of a fibrin clot. A thrombotic episode was seen in one elderly (71-year-old) patient after aspirin discontinuation during long-term immobilization. Conclusion. Nearly 50% of the primary patients with MM were ascertained to be more prone to thrombosis. Infusion of unfractionated heparin in a dose of 500 U/hr or administration of aspirin (100 mg/day) was the adequate prevention of thrombotic events.

AIM. To determine the frequency and pattern of blood clotting disorders in patients with multiple myeloma (MM) and to evaluate the adequacy of preventive anticoagulant or antiaggregant therapy. MATERIALS AND METHODS. The prospective study conducted at the Department for High-Dose Chemotherapy and Bone Marrow Transplantation, Hematology Research Center, Ministry of Health of the Russian Federation, in March 2012 to May 2013, enrolled 25 patients (13 men and 12 women) aged 29-72 years (median age 54 years) with new-onset MM. The latter was staged using the Durie-Salmon classification: Stages I, II, and III were determined in 2, 10, and 13 patients, respectively. Seven patients were found to have renal dysfunction (which corresponded to Substage B). The hemostasis was evaluated from the results of the following tests: activated partial thromboplastin time (APTT), thrombin time (TT), XIIa-dependent fibrinolysis time, Quick prothrombin index, international normalized ratio (INR), and fibrinogen and D-dimer concentrations. The investigators used new hemostatic techniques, such as thrombin generation test, thromboelastography, as well as thrombodynamics, a novel method to determine the characteristics of spatial clot growth. Induction therapy was performed using the PAD and VCD regimens. Thromboses were prevented by using 24-hour infusion of unfractionated heparin (500 U/hr) or by administering aspirin (100 mg/day). RESULTS. Hypercoagulability was identified in 17 (68%) patients. Eleven (44%) patients had elevated D-dimer concentrations. The level of D-dimer was statistically significantly positively correlated with the endogenous thrombin potential and the amount of Β2-microglobulin. The thrombodynamic technique revealed an inverse relationship between the level of paraprotein and the optimal density of a fibrin clot. A thrombotic episode was seen in one elderly (71-year-old) patient after aspirin discontinuation during long-term immobilization. CONCLUSION. Nearly 50% of the primary patients with MM were ascertained to be more prone to thrombosis. Infusion of unfractionated heparin in a dose of 500 U/hr or administration of aspirin (100 mg/day) was the adequate prevention of thrombotic events.

Case report of a patient developed deep neutropenia and severe infectious complications after chemotherapy is presented. Lasting aplasia after a course of chemotherapy, life-threatening infectious complications did not allow pretransplantation conditioning with standard immunosuppression because of extremely high risk of a lethal outcome. Allogenic bone marrow transplantation from a related donor was carried out. lmmunosuppression was carried out only with cyclophosphamide (50 mg/kg on day,3 after transplantation) and mesenchymal stromal cells. Transplant healing (WBC > 1 center dot 109/l) was diagnosed on day 19. The patient was discharged 3 months after transplantation. 12 months after bone marrow transplantation a 100% donor chimera persists. This case report is the first report about effective bone marrow transplantation without pretransplantation conditioning in a patient with acute leukemia and lasting aplasia after chemotherapy.

AIM:To determine the frequency and pattern of blood clotting disorders in patients with multiple myeloma (MM) and to evaluate the adequacy of preventive anticoagulant or antiaggregant therapy.SUBJECTS AND METHODS:The prospective study conducted at the Department for High-Dose Chemotherapy and Bone Marrow Transplantation, Hematology Research Center, Ministry of Health of the Russian Federation, in March 2012 to May 2013, enrolled 25 patients (13 men and 12 women) aged 29-72 years (median age 54 years) with new-onset MM. The latter was staged using the Durie-Salmon classification: Stages I, II, and III were determined in 2, 10, and 13 patients, respectively. Seven patients were found to have renal dysfunction (which corresponded to Substage B). The hemostasis was evaluated from the results of the following tests: activated partial thromboplastin time (APTT), thrombin time (TT), Xlla-dependent fibrinolysis time, Quick prothrombin index, international normalized ratio (INR), and fibrinogen and D-dimer concentrations. The investigators used new hemostatic techniques, such as thrombin generation test, thromboelastography, as well as thrombodynamics, a novel method to determine the characteristics of spatial clot growth. Induction therapy was performed using the PAD and VCD regimens. Thromboses were prevented by using 24-hour infusion of unfractionated heparin (500 U/hr) or by administering aspirin (100 mg/day).RESULTS:Hypercoagulability was identified in 17 (68%) patients. Eleven (44%) patients had elevated D-dimer concentrations. The level of D-dimer was statistically significantly positively correlated with the endogenous thrombin potential and the amount of beta2-microglobulin. The thrombodynamic technique revealed an inverse relationship between the level of paraprotein and the optimal density of a fibrin clot. A thrombotic episode was seen in one elderly (71-year-old) patient after aspirin discontinuation during long-term immobilization.CONCLUSION:Nearly 50% of the primary patients with MM were ascertained to be more prone to thrombosis. Infusion of unfractionated heparin in a dose of 500 U/hr or administration of aspirin (100 mg/day) was the adequate prevention of thrombotic events.