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.

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.

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.

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.

To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.

Addition of cladribine to induction/consolidation regimen does not impair peripheral blood stem cell mobilization and bone marrow harvest for autotransplantation in acute myeloid leukemia patients.

BACKGROUND: The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation. PATIENTS AND METHODS: Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy. RESULTS: The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups. CONCLUSION: Addition of cladribine to a standard DA induction does not impair the harvesting of hematopoietic cells and their engraftment after autotransplantation.

Triple transplantation of autologous peripheral blood stem cells each time following conditioning with 100 mg/m2 of melphalan for multiple myeloma patients in poor performance status.

Approximately one third of multiple myeloma patients (below 60 years) are diagnosed either in advanced disease or with significant comorbidities. Many other patients referred to transplant centers have already been heavily pretreated with multiple courses of various conventional chemotherapies. These patients are frequently in bad or even grave clinical condition; they are unlikely to survive standard high-dose melphalan (200 mg/m(3)) chemotherapy and autologous hematopoietic stem cell transplantation. Palumbo et al reported a protocol for elderly patients that utilized reduced conditioning (melphalan 100 mg/m(2) three times at 2-month intervals, each time supported by autologous hematopoietic rescue). We have used this protocol as a start to develop a method to induce a remission in the aforementioned subgroup of myeloma patients. Patients with stage III disease and WHO performance status 2 or higher are treated with one or two cycles of cyclophosphamide (2 to 4 g/m(2)) and undergo peripheral blood stem cells collection. Subsequently, they are treated with three to four doses of melphalan (100 mg/m(2)) at 8- to 12-weeks intervals each time supported by infusion of peripheral blood stem cells. To date 13 patients have been entered into the protocol. With one exception of transiently stable disease, the remaining patients obtained at least partial remission and three, complete remission. The compliance was good and better with each subsequent course. For half of the patients the problem was a short duration of response. This method when developed may offer a new treatment alternative for a subgroup of high-risk multiple myeloma patients.

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.

Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR-ABL--positive acute lymphoblastic leukemia-retrospective analysis of Polish Adult Leukemia Group (PALG).

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.

[Chloroma--a rare symptom of acute leukemia]. / Zieleniak (chloroma)--rzadki objawy ostrej bialaczki.

Chloroma is a tumour composed of immature granulocytes localized in extramedullary tissues. Chloroma is noted in the course of the acute non-lymphoblastic leukemia (ANLL), chronic myeloid leukemia (CML), and in myelodysplastic syndromes (MDS) during their transformation in the acute leukemias. Due to chloroma infrequency, two cases seen at the Department of Hematology, Medical Academy in Warsaw are presented. A survey of the actual literature is included.

[Erythropoietin in the pathogenesis of anemia in patients with multiple myeloma]. / Erytropoetyna w patogenezie niedokrwistosci u chorych na szpiczaka mnogiego.

UNLABELLED: Anemia is a common symptom in multiple myeloma (MM) patients but the pathogenesis of it is still unknown. The aim of the study was to explain the causes of anemia in MM patients. Peripheral blood count, bone marrow aspirate, iron and ferritin level, serum erythropoietin (EPO) level, T cell subsets and in vitro CFU-E count were analyzed in the group od 31 MM patients. Erythropoietin and iron deficiency in the study group were not observed. EPO serum level was not significantly different in patients with multiple myeloma and in comparison to patients with sideroblastic anemia with solid tumors. Absolute CD8 T lymphocyte count was not significantly increased in the study group. CFU-E colonies count in vitro was not decreased in these patients. CONCLUSIONS: In the study group of the MM patients anemia probably does not depend on EPO production. Diminished proliferative response of erythropoietic cells on normal serum level of EPO and abnormal iron utilisation probably occur in these patients. Replacement of normal erythropoiesis by tumor plasma cells is probably not decisive.

[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.

[Bone mineral disorders in patients with multiple myeloma]. / Zaburzenia mineralizacji kosci u chorych na szpiczaka mnogiego.

The aim of the study was to evaluate bone mineralization in the patients with multiple myeloma. The examinations were performed in 49 patients (25 men and 24 women). Seven patients were before chemotherapy and 42 patients were treated with chemotherapy. All of them received prednisone. The bone mineral density was measured by dual-energy X-ray absorptiometry with Lunar spine (L2-L4) in AP projection, femoral neck and total body were examined. There was a decrease of bone mineral density in 35 patients in at least one place (T-score more than 2 SD below normal of young healthy persons). There was no correlation between densitometric results and the duration of multiple myeloma, or chemotherapy. The decrease of bone mineral density (expressed es T-score) of lumbar spine (for the patients without spinal degenerative changes) was higher than that of femoral neck (p < 0.05). The decrease of bone mineral density (expressed as T-score) of lumbar spine and femoral neck was more pronounced than that of total body (p < 0.001). Bone densitometry, especially of lumbar spine and femoral neck and less of total body is indicated in the patients with multiple myeloma. The result of this examination may be considered as an independent parameter of disease intensity.

[Effect of calcitonin treatment on bone mineralization in patients with multiple myeloma]. / Wplyw leczenia kalcytonina na mineralizacje kosci u chorych na szpiczaka mnogiego.

The aim of the study was to evaluate the efficacy of half-year treatment of bone mineral disturbances with calcitonin in the patients with multiple myeloma. Thirty five patients (11 men and 24 women) were examined. They were treated among other with prednisone. Nineteen patients (15 patients with normal bone mineral density of lumbar spine and femoral neck and 4 with low bone mineral density who could not be treated with calcitonin) were treated only with chemotherapy. Other 16 patients with low bone mineral density have received also calcitonin (100 units subcutaneous daily) with vitamin D3 and calcium carbonate. Bone mineral density was evaluated with dual energy X-ray absorptiometry in lumbar spine and femoral neck. After treatment with calcitonin there was more pronounced influence on bone mineral density in lumbar spine and femoral neck than after treatment with chemotherapy only but the difference was not statistically significant. Because the bone mineral disturbances in the patients with multiple myeloma is the big problem there is a need for further and longer evaluation of the treatment of these disturbances.