Azacitidine for Relapse After Allogeneic Stem Cell Transplantation-Single-Center Study.

BACKGROUND: Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine is one of the available options. METHODS: This was a retrospective, single-institution study. Of 28 evaluated patients, 18 were males, and the median age was 60 years (range, 15-78). There were 15 patients with acute myeloid leukemia, 8 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 1 with primary myelofibrosis. Ten patients received azacitidine for overt relapse, 14 received it as a preemptive therapy, and 4 others received it as maintenance treatment after allo-hematopoietic cell transplant (HSCT). Eleven patients received a donor lymphocyte infusion (DLI). RESULTS: The patients received median 5 (1-9) cycles of azacitidine in preemptive and maintenance therapy and median 2.5 (1-9) cycles in patients with relapse. Thirty-nine percent of patients received DLIs. Median overall survival was 6.1 months (95% CI, 0.7-13) for relapse therapy vs 21.2 months (95% CI, 8.4-inf) for preemptive therapy. Among patients treated for relapse, 30% achieved temporary disease control and underwent the second allo-HSCT. A complete, cytogenetic remission was achieved in 50% of patients and stable minimal residual disease in 14% of patients in a group with preemptive therapy. Toxicity was considerable; neutropenia (71%), anemia (14%), thrombocytopenia (36%), and serious infections (36%) were observed in the preemptive setting. CONCLUSIONS: These data support the notion that azacitidine is best used as a preemptive therapy against relapse for patients after allo-HSCT performed for myeloid malignancy. Applying azacitidine as therapy for ongoing relapse after allo-HSCT may lead to stable disease and allow for better performance of the second allo-HSCT.

Pericarditis in Patients With Chronic Graft-vs-Host Disease.

BACKGROUND: There are only a few cases of pericarditis complications following allogeneic bone marrow transplantation described in the literature and there are no data available on the risk and frequency of this condition. The aim of this study was to assess the frequency of exudative pericarditis complicating chronic graft-vs-host disease in allogeneic hematopoietic cell transplant recipients. METHODS: Retrospective analysis involved a group of 105 patients of the Outpatient Transplantation Service of the Department of Hematology, Medical University of Warsaw, who received transplants in the years 2010-2016 and were evaluated for the years 2014-2016. In this group, 50 patients suffered from chronic graft-vs-host disease (cGVHD), including 24 with moderate or severe disease. Cardiology parameters evaluated included electrocardiography, echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and systematic clinical follow-up. RESULTS: Pericarditis was diagnosed in 6 patients (aged 20-56 years) within 4 to 23 months after allogenic hematopoietic stem cell transplantation. All patients suffered from severe cGVHD with involvement of at least 2 organs but none had earlier history of heart disease. All patients had elevated NT-proBNP and demonstrated signs of heart insufficiency grade II or III according to the New York Heart Association. There were no major changes in electrocardiogram. Only 1 patient improved following glucocorticosteroids as monotherapy, while others required complex approaches including tacrolimus plus sirolimus, rituximab, and extracorporeal photopheresis. CONCLUSION: Late pericarditis may occur in up to 5% of allogenic hematopoietic stem cell transplantation survivors, primarily affecting patients with moderate and severe grade cGVHD. It requires escalation of immunosuppressive treatment but usually has favorable outcome. Early diagnosis may be achieved by systematic NT-proBNP testing and periodic echocardiograph evaluation.

Immunoablation and autologous hematopoietic stem cell transplantation in the treatment of new-onset type 1 diabetes mellitus: long-term observations.

The activity of the autoimmune mechanism underlying type 1 diabetes mellitus (T1DM) can be suppressed when immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) are applied early in the course of the disease. We report here a single centre experience with this treatment modality. Twenty-four patients underwent a AHSCT preceded by immunoablative conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. During the 52-month median time of follow-up 20 out of 23 patients (87%) remained for at least 9.5 months without the use of exogenous insulin. The median time of T1DM remission for these patients was 31 months (range of 9.5-80 months). Among the patients available for follow-up (n=20), four remain insulin free (for 80, 61, 42 and 34 months). The average glycated hemoglobin (HbA1c) concentrations were 10.9% at diagnosis, 5.9% at 1 year, 6.4% at 2 years, 6.8% at 3 years and 7.1% at 4 years after AHSCT. No severe complications of diabetes were seen, however one of the patients died of pseudomonas sepsis in the course of neutropenia after AHSCT. AHSCT leads to a remission of T1DM with good glycemic control in the vast majority of patients, with the period of remission lasting over 5 years in some patients.

High-dose melphalan and autologous hematopoietic stem cell transplantation in primary amyloidosis: single-center results.

BACKGROUND: Systemic immunoglobulin light-chain amyloidosis (AL) is a plasma cell dyscrasia resulting in multisystem organ failure and death. Autologous hematopoietic stem-cell transplantation (ASCT) has been widely used to treat patients with AL. However, treatment-related mortality remains high and reported series are subject to selection bias. METHODS: To define the role of patient selection in stem cell transplantation, we evaluated 24 consecutive AL patients transplanted at our center. RESULTS: Complete hematologic response was achieved in all 20 patients surviving >100 days posttransplantation. The 1-year overall survival (OS) rate after ASCT was 78.5%. The 5- and 10-year progression-free and OS rates were 57% and 47%, respectively. Treatment-related deaths owing to cardiovascular problems occurred in 16% of cases. CONCLUSION: ASCT for AL amyloidosis can be safely performed in experienced transplantation centers, and increased risk is associated mainly with cardiovascular system involvement.

Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I.

Type I diabetes mellitus is a metabolic disease caused by chronic immune attack against the insulin-producing cells of the pancreas. It has recently been shown that the clinical course of this disease can be interrupted by immune ablation and PBSCT. In this report, we describe our experience with this treatment modality in a series of eight cases. Patients with newly diagnosed type I diabetes were received treatment consisting of two to three plasmaphereses, hematopoietic stem cell mobilization with CY and G-CSF, collection of at least 3 × 10(6) per kg of CD34+ cells, and conditioning with CY and anti-thymocyte globulin followed by stem cell infusion. All patients became independent of exogenous insulin after the transplantation. One patient resumed low-dose insulin 7 months after transplantation. Six out of eight patients were given acarbose for better glycemic control after transplantation. All patients exhibited good glycemic control: the average HbA1c concentrations were 12.3% at diagnosis, and 5.6 and 6.2% at 3 and 6 months after transplantation, respectively. We conclude that at least temporary independence of exogenous insulin can be achieved in type I diabetes patients following immunoablation and reconstitution of the immune system with autologous PBSCs.

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia.

The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m2 on day 1 and cyclophosphamide at 650 mg/m2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P= 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation.

Activity of 2-chlorodeoxyadenosine (Cladribine) in 2-hour intravenous infusion in 94 previously treated patients with low grade non-Hodgkin's lymphoma.

The purpose of our study was to determine the efficacy of 2-chlorodeoxyadenosine (2-CdA) administered in 2-hour intravenous infusions in previously treated patients with low grade non-Hodgkin's lymphoma (LGNHL). We treated 94 LGNHL patients with 2-CdA at a dosage of 0.12 mg/kg/24h in 2-hour intravenous infusion for 5 consecutive days. The treatment consisted of from 1 to 7 courses (median 3), repeated usually at monthly intervals. All patients were refractory to or relapsed after standard chemotherapy. Of these 94 patients 78 (83%) had clinical stage IV of the disease. Complete response (CR) was obtained in 12 (12.8%) and partial response (PR) in 36 (38.3%) giving an overall response rate of 51.1%. In 12 (12.8%) grade 4 thrombocytopenia with haemorrhagic diathesis was noted, grade 4 neutropenia was observed in 12 (12.8%) and infections complicated the course of treatment in 38 (40.4%) patients. 2-CdA treatment was the cause of death of 3 patients. The results of our study show that 2-CdA given in 2-hour infusions is an effective agent in advanced, heavily pretreated patients with LGNHL.

[Nocturnal paroxysmal hemoglobinuria--case report]. / Nocna napadowa hemoglobinuria--opis dwóch przypadków.

Paroxysmal nocturnal hemoglobinuria (PNH)-a case report. We present clinical and postmortem findings in patient with PNH who developed cerebral thrombosis. The pathogenesis of the PNH is discussed.

[Perforation in the gastrointestinal tract as a complication of acute leukemia]. / Perforacja w obrebie przewodu pokarmowego jako powiklanie ostrej bialaczki.

Two cases of gastrointestinal perforation in patients with acute leukemia are reported. They were thrombocytopenic, but successfully surgically treated.

[Cerebral thrombosis in paroxysmal nocturnal hemoglobinuria: case report]. / Przypadek zakrzepicy naczyn mózgowych w przebiegu nocnej napadowej hemoglobinurii.

Clinical, radiological and postmortem findings in a 25-year old woman with paroxysmal nocturnal hemoglobinuria (PNH) who developed cerebral thrombosis are presented. The pathogenesis of the PNH is discussed.