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BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains the most efficacious therapy in patients with acute leukemia. For older patients and those lacking a related HLA-compatible donor, autologous transplantation (auto-HSCT) is a valid alternative therapeutic option. METHODS: From 1997 until 2014 in the Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Poland, 29 auto-HSCT were performed in patients with acute myeloid leukemia (AML; 15 men and 14 women; median age, 52.2 years). The following FAB types of AML were diagnosed: M0, 3; M1, 4; M2, 6; M4, 10; and M5, 6. Patients with AML were classified into 3 cytogenetic prognostic groups: high risk, 9; intermediate risk, 16; and low risk, 4. Twenty-five were in first complete remission and 4 in second complete remission. The peripheral HSCs mobilized after chemotherapy (mainly second course of consolidation) and granulocyte colony-stimulating factor were the source of the stem cells in all cases. The median number of infused CD34+ cells was 3.58 × 10(6)/kg. The conditioning regimen was busulfan and cyclophosphamide in all patients with AML. The intravenous form of busulfan was applied in the last 15 patients. RESULTS: The median time for absolute neutrophil count recovery >0.5 × 10(9)/L and for platelet count >20.0 × 10(9)/L was 12 and 16.5 days, respectively. Treatment-related mortality rate in the whole group was 3.4% (1 patient with sepsis in the aplastic period). The median follow-up time of survivors was 21.9 months (range, 11.7-142.4). The 3-year projected disease-free survival and overall survival rates were 60% and 68%, respectively. CONCLUSIONS: Our data confirm that auto-HSCT is a valuable therapeutic option for patients with AML, especially older patients and those lacking related HLA-compatible donors.

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BACKGROUND: Autologous peripheral blood stem cell transplantation (APBSCT) is the standard of therapy for patients with multiple myeloma and refractory Hodgkin's and non-Hodgkin's lymphomas. Granulocyte colony-stimulating factor (G-CSF) is widely used to accelerate hematopoietic recovery after transplantation and to reduce the morbidity and mortality associated with prolonged neutropenia. Biosimilar G-CSF is approved for the same indications as the originator G-CSF. This is one of the first reported uses of a biosimilar G-CSF for neutrophil recovery after APBSCT. METHODS: A total of 23 consecutive patients with hematological malignancy (multiple myeloma, Hodgkin's and non-Hodgkin's lymphomas, and acute myelogenous leukemia) were recruited at the Department of Haematooncology and Bone Marrow Transplantation at the Medical University of Lublin. Patients (12 men and 11 women; median age, 47 ± 13 years) received biosimilar G-CSF (Zarzio, Sandoz Biopharmaceuticals) after myeloablative chemotherapy (primarily BiCnU, etoposide, cytarabine, and melphalan or melphalan 140/200 mg/m(2)) followed by PBSCT. The median number of transplanted CD34+ cells was 4.2 ± 0.8 × 10(6)/kg body wt. G-CSF therapy was started when absolute neutrophil count (ANC) was <0.5 × 10(9)/L and was continued until ANC reached >1.5 × 10(9)/L for 3 consecutive days. Hematopoietic recovery parameters were compared with those in the control group, which consisted of 23 consecutive patients transplanted in the period before the biosimilar G-CSF group and receiving originator G-CSF (Neupogen, Amgen). RESULTS: The mean duration of treatment with biosimilar and originator G-CSF was 14.4 ± 5.1 and 18.6 ± 11.5 days, respectively (P = .43). The adverse event profile was comparable between the biosimilar G-CSF and originator G-CSF groups, with similar occurrence of neutropenic fever (5 versus 6 patients) and bone pain (7 patients in each group). One patient in the biosimilar group had neutropenic enterocolitis and sepsis. There was no case of death in either group. Granulocyte recovery in the study group was as follows: mean days to ANC >0.5 × 10(9)/L was 13.0 ± 4.0 days; to ANC >1.5 × 10(9)/L, 13.6 ± 4.5 days; and to ANC >1.5 × 10(9)/L, 14.0 ± 4.7 days. Mean duration until platelet recovery >20 × 10(9)/L was 16.1 ± 4.4 days. There were no statistically significant differences between the biosimilar and originator G-CSF groups in hematopoietic recovery parameters. CONCLUSIONS: Biosimilar G-CSF is safe and effective in reducing the duration of neutropenia in patients undergoing myeloablative therapy followed by APBSCT and probably in cost savings in transplantation budgets.

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The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed multiple myeloma (MM) patients who have a long-term response to thalidomide (THAL), lasting at least 18 months. The study was carried out on 234 patients who received THAL for relapsed/refractory myeloma. Out of the 234 patients, 129 patients (55.1%) responded to THAL with a mean response duration of 11.9 months (ranging from 1 to 48) and an overall survival rate of 20.3 months (ranging 1-55 months). In 64 patients (27.4% of the whole group), the response to THAL lasted > or =18 months with a mean response lasting 24 months. Statistical analysis of the group of nonresponders and patients with long-term response to THAL showed a significantly higher serum albumin level (P=0.0003) and haemoglobin level (P=0.05), as well as a lower beta2 microglobulin (beta2M) (P=0.022), LDH (P=0.045) serum level in patients with long-term response. In this study, the LDH and serum albumin level were predictors for response to THAL therapy. The beta2M serum level was not a predictor for response to THAL. The albumin serum level was the best parameter distinguishing the group of patients with long-term response to THAL from the entire responding group (P=0.02).

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BACKGROUND AND OBJECTIVES: Thalidomide is currently used as a very promising drug in patients with recurrent multiple myeloma or those refractory to chemotherapy. Literature data show prolonged survival in patients with advanced multiple myeloma treated with thalidomide but the optimal time and dose of thalidomide treatment remain to be established. DESIGN AND METHODS: We have treated 53 refractory or relapsed myeloma patients with thalidomide (Grunenthal, Aachen). The patients received thalidomide orally as monotherapy at a starting dose of 200 mg daily, with a dose increase of 100 mg every week to a maximum well-tolerated dose of 400 mg. All the patients qualified for the therapy underwent clinical and laboratory assessments every 4 weeks. Laboratory tests included complete blood count, electrophoresis, immunoglobulin level, lactate dehydrogenase (LDH), C-reactive protein, b2 microglobulin concentration, liver and renal function tests and there was also a monthly neurological examination. Bone marrow aspiration was performed every 3 months during the 12-month treatment. RESULTS: Among 53 evaluable patients, a clinical response was observed in 27 (51%): there was a major response in 7 patients, a partial response in 12 and a minor response in 8. INTERPRETATION AND CONCLUSIONS: In responding patients the earliest response was observed after 4 weeks of treatment and the latest after 12 weeks of treatment. Our results, obtained during a long observation period, show that thalidomide is an effective drug, with an acceptable degree of toxicity, in patients with refractory multiple myeloma.

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Supernatants from short-term culture of peripheral blood and bone marrow mononuclear cells obtained from 22 multiple myeloma patients were used to measure the concentration of TNF-alpha, HGF, IL-6 and its soluble receptor (sIL-6R), VEGF and bFGF. Cells were cultured with or without thalidomide (THAL). We observed statistically significant decrease in TNF-alpha, HGF, IL-6, sIL-6R in supernatants from THAL cultures compared to cells cultured without THAL. Flow cytometry technique was applied to study the Bcl2 expression on CD 4, CD 8 and CD 138 positive cells. The statistically significant decrease in Bcl2 expression on myeloma cells (CD 138+) was observed both in PB and BM cultures. THAL could inhibit the plasma cell growth both by diminishing proangiogenic cytokines production and enhancing myeloma cell apoptosis.

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We describe here a patient with multiple myeloma, who, while in remission after chemotherapy, received 100 micrograms of rIFN-gamma (Imukin, Boehringer, Ingelheim) subcutaneously 3 times a week for 4 weeks as supportive therapy before autologous peripheral blood stem cell transplantation (PBSCT). The patient was monitored for serum IFN, TNF, IL-2 activities and for the ability of peripheral blood leukocytes (PBL) to produce IFN-alpha/beta, IFN-gamma, IL-2 and TNF-alpha after in vitro induction. Changes in the percent of plasma cells in the bone marrow, in the total and differential white blood cell counts, in T cell subsets and NK cells were also monitored. IFN-gamma yielded no clinical antitumor activity. The number of bone marrow plasma cells increased, however, the percentage of blood and bone marrow NK cells and the CD4/CD8 T cell subset ratio decreased. Monitoring the cytokine production ability of PBL during IFN-gamma therapy revealed an increase in IL-2, IFN-gamma and TNF-alpha titers produced upon in vitro induction after 2 weeks of treatment (6 injections of rIFN-gamma). However, after 9 injections there was a significant decrease in IFN-gamma and IL-2 production in the PBL, and at the end of therapy (12 injections) the decrease not only in IL-2 and in IFN-gamma but also in IFN-alpha production was observed. In contrast to these changes, TNF production was strongly enhanced and reached the level observed before the therapy. These data suggest that the schedule of IFN-gamma therapy in multiple myeloma should perhaps be adapted to become more effective, taking advantage from the immunomodulating activity of IFN-gamma.

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Clinical features of multiple myeloma are linked with immunological phenotype of myeloma cells. The interactions between malignant plasma cells and proteins of ECM (extracellular matrix) or different cells results from the influence of adhesion molecules. In our study the expression of CD49b, CD49d, CD49e, CD49f on the myeloma cells has been estimated. These cells were obtained from bone marrow of 33 just diagnosed patients. Immunophenotyping was performed with flow cytometry method. Malignant plasma cells were identified by monoclonal antibody anti-CD138 (B-B4) directed against Syndecan-1. We have observed that in patients with high expression of laminin receptors CD49b, CD49f and lack of fibronectin receptors CD49d, CD49e more often renal failure has been confirmed.

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