Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas - a single centre experience.

BACKGROUND: Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. PATIENTS AND METHODS: Seventeen patients with FL and 29 patients with MCL were included, 15 of them were transplanted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. RESULTS: The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%-96.8%) and for MCL 79.3% (95% CI 56.1%-91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%-90.3%) and for MCL 69.8% (95% CI 45.5%-84.8%), respectively. There were no secondary hematological malignancies observed in either group. CONCLUSIONS: Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies.

Citrate anticoagulation during post-dilution hemodiafiltration with a high cut-off (Theralite) membrane.

Citrate anticoagulation has not yet been described for hemodiafiltration (HDF) with high cut-off (HCO) membranes, which can be used in the treatment of cast nephropathy secondary to multiple myeloma. A 57-year-old male patient with multiple myeloma and acute renal failure was treated with HDF using a HCO membrane (Theralite) each or every other day. Due to thrombocytopenia, citrate anticoagulation was done for the first 7 h, and anticoagulant-free HDF was performed for the last hour to avoid citrate accumulation. Magnesium, phosphate, and albumin were measured after 3, 6, and 8 h, and were replaced as necessary. Thirty-two post-dilution HDF procedures (8 h each, infusate 24 L) were performed with blood flow at 300-330 mL/h; sodium citrate 4% was infused at 300 mL/h and 1 mol/L calcium chloride was infused at a mean rate of 14.6 ± 1.1 mL/h. Calcium-free dialysate/infusate was used. Ionized calcium was stable (1.10 ± 0.06 before and 1.08 ± 0.06 mmol/L after HDF). Magnesium was stable (0.67 ± 0.12 before and 0.68 ± 0.05 mmol/L after HDF), with an average 390 ± 180 mg per procedure, substituted orally. There was no metabolic alkalosis or hypernatremia after the procedures, and no significant clotting was noted. The total/ionized calcium ratio (1.87 ± 0.22 before vs. 1.56 ± 0.20 after 6 h) and the corrected/ionized calcium ratio (2.02 ± 0.21 before vs. 1.88 ± 0.27 after 6 h) decreased during HDF, indicating no citrate accumulation. Citrate anticoagulation was effectively performed during 8 h of HCO membrane HDF. There were no side effects of citrate anticoagulation, nor were any signs of citrate accumulation noted.

Outcome of HLA-matched related allogeneic hematopoietic stem cell transplantation for patients with acute leukemia in first complete remission treated in Eastern European centers. Better results in recent years.

The goal of this study was to analyze results and to determine factors affecting outcome of HLA-matched hematopoetic stem cells transplantation (MRD-HSCT) for patients with acute leukemia transplanted in first complete remission in Eastern European countries. Six hundred forty HSCT were performed between 1990 and 2006 for adults with acute myeloid (n = 459) and lymphoblastic (n = 181) leukemia. Two-year leukemia-free survival (LFS), nonrelapse mortality (NRM), and relapse incidence were 58 +/- 2%, 19 +/- 2%, and 23 +/- 2%, respectively. The cumulative incidence of NRM decreased from 22 +/- 2% for patients treated between 1990 and 2002 to 15 +/- 3% for transplantations performed between 2003 and 2006 (p = 0.02), despite increasing recipient age. In a multivariate analysis, time of HSCT affected both NRM and LFS. Among other prognostic factors, the use of TBI decreased relapse incidence and increased the LFS rate. We conclude that results of MRD-HSCT for acute leukemia in Eastern Europe improved over time as a consequence of decreased NRM. The use of TBI containing regimens appears advantagous.

Splenectomy for severe autoimmune cytopenias after allogenic stem cell transplantation: case report.

Autoimmune cytopenias are rare but serious complications after hematopoietic stem cell transplantation (HSCT). We per-formed splenectomy in 2 patients who had severe autoimmune cytopenias after allogeneic HSCT (allo-HSCT) that were resist-ant to immunosuppressive treatment. The first patient underwent unrelated allo-HSCT for chronic granulocytic leukemia(CGL) in July 2000. Seven months later, red blood cell and platelet counts went down. The results of a direct Coombs test were intermittently positive. The patient was resistant to therapy with steroids and high-dose immunoglobulin. After a splenectomy was performed in February 2001, the hemoglobin concentration and platelet count improved. Her blood counts remained stable, with a hemoglobin level of approximately 110 g/L and a platelet count >100 x 109/L. She continued therapy with itraconazole, valacyclovir, and penicillin. Some months later, the patient was readmitted for fulminant septic infection, which had a fatal outcome. The second patient underwent related allo-SCT for CGL in January 2003. Seven months later, he was readmitted for intraocular bleeding accompanied by severe thrombocytopenia with antiplatelet antibodies. The patient was resistant to steroid and high-dose immunoglobulin therapy. A splenectomy was performed in September 2003. His platelet count normalized and remains stable. The patient continues therapy with itraconazole, valacyclovir, and penicillin and has not experienced any serious infection. We assume that splenectomy is an effective treatment for resistant immune cytopenias after allo-HSCT. However, severe late infections can compromise the outcome.

Cell markers in the recognition of acute myeloblastic leukaemia subtypes.

The diagnosis of acute myeloblastic leukaemia (AML) is based on cell morphology, cytogenetic and molecular changes, cell markers and clinical data. Our aim was to establish whether morphology and cell markers are comparable in the evaluation of AML. Bone marrow smears were analysed, and flow cytometry and monoclonal antibodies were used to determine cell type and maturity. Morphology and cell markers correlated differently in different AML subtypes.

Effects of molgramostim, filgrastim and lenograstim in the treatment of myelokathexis.

Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 × 109/L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 µg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 µg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.