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.
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.
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.
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 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.
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 x 10(9)/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 microg/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 microg/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.
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.
Autoimmune cytopenias are rare but serious complications after hematopoietic stem cell transplantation (HSCT). We performed splenectomy in 2 patients who had severe autoimmune cytopenias after ...allogeneic HSCT (allo-HSCT) that were resistant 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.
Allogeneic BMT is treatment of choice for acute leukaemias(AL) and chronic granulocytic leukaemia (CGL). In the period form 1989 till 1997 36 allogeneic BMT have been performed for patients with AML, ...ALL and CGL using HLA matched related donors in University Medical Centre Ljubljana. The procedure was successful in 80% of patients with CGL and in 50% of patients with AL. The most frequent cause of death in CGL patients was CMV pneumonitis, relapse in patients transplanted for ALL, while in patients transplanted for AML beside relapse we observed four deaths due to complications of BMT ( acute GVHD, VOD, thrombotic thrombocytopenic purpura, liver failure due to hepatitis).
Abstract 4895
Burkitt’s lymphoma (BL) is a rare condition accounting between 1– 5% of Non Hodgkin’s lymphomas. Standard treatment consists of intensive chemotherapy with fractionated alkylating ...agents and cell cycle phase specific agents that cross the blood brain barrier. Patients who achieve only partial response after front-line treatment or in first relapse can be treated with autologous stem cell transplantation (SCT) or in rare cases with allogeneic SCT. Rituximab added to various chemotherapy regimens can improve the results. Ofatumumab is a new anti-CD20 monoclonal antibody active in refractory or high risk patients with chronic lymphocytic leukemia (CLL). We present a patient with refractory BL after standard chemo/immunotherapy and autologous SCT who achieved remission after ofatumumab treatment.
A 31-year old male patient was diagnosed with Burkitt's lymphoma (stage IIIb) in April 2011. He was put on BMF protocol but progressed after two cycles. Rituximab was added in therapy. After two additional cycles there was no response to treatment. A salvage protocol DA-R-EPOCH was employed and after four cycles patient went into partial remission. Stem cell mobilization was performed with rituximab/cyclophosphamide/filgrastim and plerixafor because of poor initial mobilization result. In September 2011 patient received autologous SCT after BEAM conditioning. Six weeks after the procedure assessment of disease showed presence of 0.14 % BL cells on bone marrow flow cytometry and residual disease in abdomen on PET-CT. The patient started with ofatumumab according to protocol used in CLL and began with local radiotherapy. After seven weeks on ofatumumab bone marrow showed no residual BL on flow cytometry. Due to high risk disease and poor graft function after autologous SCT we decided for additional allogeneic SCT which was performed in January 2012 after myeloablative conditioning with cyclophosphamide and total body irradiation. The donor was a 9/10 HLA match. Post transplant period was complicated with cytomegalovirus reactivation and side effects of cyclosporine. On day +66 the patient presented with Pneumocystis carinii pneumonia that required ventilation support. Bone marrow examination in April 2012 showed no residual BL. After short improvement the patient's condition was complicated with secondary pneumonia, acute respiratory distress syndrome and septic shock. The patient expired on day +94 after allogeneic SCT.
Ofatumumab induced remission in a patient with refractory BL after two chemotherapy regimens, rituximab and autologous SCT. The patient went into remission after eleven weeks on ofatumumab CLL protocol and was able to proceed to allogeneic SCT. He remained in remission three months post SCT. The cause of patient's death was infection. Studies would be required to address ofatumumab's role in refractory BL.
Off Label Use: Ofatumumab is registered for treatment of CLL.
To improve our understanding of the regulation of circulating platelet counts (PC) by thrombopoietin (TPO), we studied serum TPO levels and PC before and after myelosuppressive chemotherapy in 12 ...patients with acute myeloid leukaemia (AML). Serum TPO levels were measured by the quantitative sandwich enzyme-linked immunosorbent assay (Quantikine, RD Systems). At the start of the induction chemotherapy, the patients had a median serum TPO level of 199 pg/ml (range 120-2,150 pg/ml), while 10 to 12 days after the end of chemotherapy, their TPO levels were substantially increased, the median value being 1,907 pg/ml (range 1,049-4,194 pg/ml). The correlation between PC and TPO was statistically significant prior to chemotherapy (p < 0.03) and insignificant after chemotherapy. As a result of chemotherapy, the patients developed aplasia; after the administration of platelet transfusions, their median PC increased to 21 x 10(9)/l (range 5-55 x 10(9)/l), while the median TPO value decreased by 300 pg/ml (range 11-1,125 pg/ml). Our results suggest that platelet mass directly regulates serum TPO levels in acute leukaemia patients prior to chemotherapy and after the administration of platelet transfusions. Serum TPO levels may also be influenced by the cytokine response during complicating infections in patients with chemotherapy-induced cytopenia.
Iron deficiency in patients with end stage renal disease (ESRD) treated by haemodialysis (HD) is difficult to diagnose. The reticulocyte hemoglobin content (CHr) and the percentage of hypochromic red ...cells (%hypo) are sensitive novel assays for the detection of functional iron deficiency in patients treated with erithropoietin (EPO). In our study thirty-nine chronically hemodialyzed patients were evaluated to determine the value of these two parameters in comparison to the conventional biochemical indicators of iron metabolism. There were significant correlations between CHr and transferrin saturation, CHr and weekly dosage of EPO, and also between %hypo and weekly dosage of EPO. Our data represent superior value of %hypo and CHr to the transferrin saturation and ferritin concentration in detecteng of iron deficiency in HD patients.
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.
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