Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

The review dwells on certain problems of mobilization and conditioning regimens, as well as autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma. The aim of the review is to determine new approaches to improve the effectiveness of the auto-HSCT

Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma

Aim. To assess the prognostic value of clinical and hematological parameters used by hematologists for risk stratification in diffuse large B-cell lymphoma (DLBCL), and to justify the need for discovering new prognostic factors. Methods. The trial included 101 patients (48 men and 53 women) with newly diagnosed DLBCL at the age of 18–80 years (median age 58 years). The patients received R-CHOP as first-line therapy. Depending on their response all patients were stratified into 4 groups: with complete response (CR; n = 58), partial response (PR; n = 15), resistance to first-line therapy (n = 19), and early relapses (ER; n = 9). Median follow-up was 22 months (range 2–120 months). Results. In terms of age influence on the efficacy of R-СНОР as first-line therapy no significant differences were established in regard to response in patients younger and older than 65 years. Statistically significant differences were observed while analyzing two parameters of International Prognostic Index (IPI; disease stage and extranodal lesions) and B-symptoms in the CR and therapy-resistant groups. With respect to the same parameters no significant differences were found in the CR and ER groups. Median 2-year disease-free survival was not achieved in patients with CR. In patients with PR it was 12 months. Median 2-year overall survival in patients with CR, PR, and ER was not achieved, and in patients with therapy-resistant DLBCL it was 10 months. Conclusion. Results of the trial confirm prognostic value of factors applied for risk stratification in DLBCL. However, variability of clinical course of the disease, especially with a low IPI score, suggests the need for new prognostic parameters associated with the course of DLBCL

Thrombopoietin Receptor Agonists in Treatment of Idiopathic Thrompocytopenic Purpura (Primary Immune Thrombocytopenia): Efficacy and Safety in Everyday Clinical Practice

Background & Aims. The use of thrombopoietin receptor agonists (aTPO-r) is a new approach to the treatment of patients with idiopathic thrompocytopenic purpura (ITP) irresponsive to other methods. Data on the efficacy and safety of aTPO-r outside the frames of clinical trials are limited. The aim of the study is to evaluate the efficacy of the therapy in the routine clinical practice as the second and subsequent lines of therapy, as well as the frequency and nature of complications of the treatment in chronic ITP patients. Methods. Data on 58 adult patients (median age: 56 years) with chronic ITP were retrospectively evaluated; 43 (74 %) of them were treated with romiplostim and 15 (26 %) patients received eltrombopag. Two or more lines of prior therapy were ineffective in 19 (33 %) patients (14 from the romiplostim group and 5 from the eltrombopag group). aTPO-r was prescribed and adjusted according to the prescription guidelines. The efficacy of the treatment was assessed based on the platelet response and the possibility of achieving a sustained response after discontinuation of the therapy. Hemorrhagic manifestations were classified according to the WHO bleeding scale. The safety assessment is conducted by identifying adverse events (AEs) and lab test abnormalities. Treatment-related adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results. The therapy with aTPO-r was effective in 49 (84 %) patients, including 36 patients (84 %) treated with romiplostim and 13 patients (87 %) with eltrombopag. The median dose to maintain a response was 3.7 mg/kg and 44 mg, respectively. A stable remission was achieved in 4 patients after discontinuation of romiplostim and 1 patient after discontinuation of eltrombopag. aTPO-r resistance was diagnosed in 9 (16 %) patients: 7 (16 %) of them were from the romiplostim group and 2 (13 %) from the eltrombopag group. Complete arrest of bleeding was achieved in 43 (88 %) responders and its reduction to grade I was achieved in the remaining 6 (12 %) of them. The most frequent AEs of romiplostim therapy were headache, arthralgia and dermatitis; and the treatment with eltrombopag caused hepatotoxicity, headache, and nausea. The severity of events did not lead to complete discontinuation of the therapy in any case. Different types of thrombotic complications were diagnosed in 3 patients (5.2 %). Conclusion. The therapy with aTPO-r is an effective and safe method for the treatment of patients with chronic ITP in the second and subsequent lines of therapy

Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality. Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis. Materials & Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m2 cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m2 vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2–4 × 106 CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer. Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 × 106/kg vs. 7.76 × 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 × 106/kg vs. 6.8 × 106/kg) significantly increased CD34+ cell count (р = 0.022). Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lenalidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred

Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients

Background. The success of autologous hematopoietic stem cell transplantation (auto-HSCT) depends on the speed of transplant engraftment which in turn is affected by the count of harvested and infused hematopoietic stem cells (HSC). Aim. To identify predictors of auto-HSCT efficacy in multiple myeloma (MM) patients under introduction of new drugs at the phase of HSC induction and mobilization. Materials & Methods. The results of auto-transplant harvesting and engraftment were retrospectively analyzed in 75 MM patients during 112 auto-HSCTs. Auto-transplants were harvested using cyclophosphamide and vinorelbine combined with granulocyte colony-stimulating factor (G-CSF) without plerixafor. Conditioning regimen included melphalan 200 mg/m2 or 140 mg/m2, and combination of tiothepa with melphalan. All patients received subcutaneous injections of G-CSF in post-transplantation period. Transplant engraftment was assessed according to absolute neutrophil count of ≥ 0.5 × 109/L, and thrombocyte count of ≥ 20 × 109/L. Results. It is established that the predictors of a high CD34+ cell count in auto-transplant are a single previous induction regimen (p = 0.0315) and administration of cyclophosphamide in mobilization regimen (р = 0.0001). Transplant engraftment period is determined by auto-HSCT serial number and amount of infused CD34+ cells. Hematopoiesis regeneration after the second auto-HSCT was accelerated by more frequent use of Mel140 (р = 0.001). Conclusion. Auto-transplant quality and engraftment period in MM patients primarily depend on the efficacy of induction therapy and the intensity of HSC mobilization regimen. Therefore, induction therapy and mobilization regimen need to be tailored to an individual patient, MM prognostic variant, probability of response to standard induction regimens, and the number of planned auto-HSCTs

Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters. Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry. Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation. Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients

Low Dose Cytarabine and Cladribine for Treatment of Relapsed or Refractory Acute Myeloid Leukemia: Clinical Experience

Aim. The aim of this paper is to evaluate the effectiveness of low dose cytarabine (Ara-C) combined with cladribine for the treatment of relapsed or refractory acute myeloid leukemia (AML) and to determine clinical and lab factors associated with response to the therapy. Methods. Data of 10 patients aged 26–58 years (median 48 years) were analyzed. The diagnoses were de novo AML (7 patients), secondary AML (sAML) (2 patients) and refractory anemia with excess of blasts (RAEB-2) (1 patient). Four patients had primary refractory AML. Relapse was diagnosed in 3 patients. The induction scheme 7+3 was ineffective in patient with RAEB-2. There was no response to any kind of therapy in sAML patients. The treatment scheme under trial consisted of Ara-C 10–15 mg/m2 subcutaneously twice a day for 1–14 days and cladribine 5 mg/m2 intravenously once a day for 1–5 days. The course was repeated in case of at least two-fold decrease in bone marrow blasts level in a punctate versus baseline. Medical examination and maintenance therapy were performed in accordance with protocols approved by the clinic. Results. According to the protocol, the patients received 1–2 courses. Response was achieved in 5 patients: 2 patients achieved complete response (CR) and 3 achieved partial response (PR). The most common complication was hematologic toxicity. All patients received transfusions of blood components. No lethal outcomes were observed within 8 weeks. The duration of the response was 2 to 3 months. During this period of time, allogeneic stem cell transplantation was performed in 2 patients with CR; however, in one patient, the conditioning regimen began at the same time with the increase in blast cell count in the bone marrow. The search for unrelated donors of hematopoietic stem cells for 2 patients with CR was begun. The distinct features of all patients with CR and PR were the following factors: de novo AML, absence of FLT3 or c-KIT mutations and the course duration was not less than 10 days. Conclusion. Low dose Ara-C in combination with cladribine may be considered a treatment option for some patients with relapsed or refractory de novo AML