Malgorzata Krawczyk-Kulis

Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study

The treatment of adults with Philadelphia‐negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4‐2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17–60 years), 116 patients were suitable for analysis. MRD level ≥0·1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0·0001), as well as in the standard risk (SR, P = 0·0003) and high‐risk (P = 0·008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0·1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0·001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.

Homozygosity for human leucocyte antigen-C ligands of KIR2DL1 is associated with increased risk of relapse after human leucocyte antigen-C-matched unrelated donor haematopoietic stem cell transplantation.

Human leucocyte antigen (HLA)‐C molecules regulate the function of natural killer cells and may be subdivided into two groups, C(1) and C(2), based on their specificity for inhibitory killer immunoglobulin‐like receptors. We analysed the impact of the HLA‐C genotype on outcome of HLA‐C‐matched unrelated donor haematopoietic stem cell transplantation (URD‐HSCT) recipients. HLA‐C(2) homozygous patients (n = 18) had lower probability of overall survival (P = 0·01) and disease‐free survival (P = 0·02), resulting from increased relapse rate (P = 0·02) when compared with both HLA‐C(1) homozygous (n = 43) and HLA‐C(1),C(2) heterozygous (n = 50) subgroups. Patients lacking HLA‐C(1) should, therefore, be considered at increased risk of relapse following HLA‐C‐matched URD‐HSCT.

Activating killer immunoglobulin-like receptor incompatibilities enhance graft-versus-host disease and affect survival after allogeneic hematopoietic stem cell transplantation.

Objectives:  Killer immunoglobulin‐like receptors (KIRs) regulate function of natural killer (NK) cells and a subset of T cells. In this study, we prospectively evaluated the impact of donor and recipient activating KIR genes on outcome of allogeneic hematopoietic stem cell transplantation (alloHSCT) for patients with hematological malignancies.

Treosulfan and fludarabine low-toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia

Allogeneic haematopoietic stem cell transplantation (alloHSCT) is the only treatment of proven long‐term efficacy in chronic myeloid leukaemia (CML), although high non‐relapse mortality (NRM) observed after conventional myeloablative conditioning limits its applicability. This phase II trial evaluated the efficacy and toxicity of a new preparative regimen consisting of treosulfan 3 × 14 g/m2 and fludarabine 5 × 30 mg/m2, in patients with CML in chronic phase. Among the 40 patients included, 18 received alloHSCT from a sibling and 22 from an unrelated donor. All patients engrafted with 92·5% of cases achieving complete donor chimaerism by day +100. All but one patient had achieved complete cytogenetic remission on day +100. Grade III or IV non‐haematological toxicities included: neutropenic fever (10%), nausea/vomiting (10%), elevated liver enzymes (5%) and infection (2·5%). The incidence of grade II–IV acute graft‐versus‐host disease (GVHD) was 22·5% and extensive chronic GVHD, 14%. The 2‐year probability of overall survival, leukaemia‐free survival and NRM was 85%, 82·5% and 15% respectively. At 1 year post‐transplant, 85% of survivors had a Karnofsky index of 100%. We concluded that treosulfan and fludarabine conditioning is a low‐toxicity regimen with high anti‐leukaemic potential that seems feasible in CML patients referred for alloHSCT.

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.

Bendamustine as monotherapy and in combination regimens for the treatment of chronic lymphocytic leukemia and non-hodgkin lymphoma: a retrospective analysis.

Background/Aim: In this study, we carried out a retrospective analysis of the efficacy and toxicity of bendamustine in patients with B-cell lymphoproliferative diseases. Methods: Bendamustine was administered both as monotherapy and in combined protocols to 92 patients, including 76 patients with chronic lymphocytic leukemia (CLL) and 16 patients with indolent lymphomas. Bendamustine plus rituximab was used to treat 65.2% of the patients, and 34.8% of the patients received bendamustine as monotherapy. Results: The overall response rate was 64.2%, including the complete response rate (18.5%) and the partial response rate (45.7%). The median overall survival (OS) was 11.5 months. Among the pretreatment parameters, β2-microglobulin (RR = 1.413; p = 0.001) and hemoglobin levels (RR = 0.85; p = 0.03) significantly influenced survival. The OS was significantly longer in patients who received ≤2 lines of previous therapy compared to >3 lines (p = 0.043; log-rank test) and those who received ≥4 courses of therapy with bendamustine (p = 0.0007; log-rank test). Toxicity was predominantly hematological, including grade III/IV neutropenia in 33.7%, thrombocytopenia in 13%, and anemia in 13% of patients. Conclusion: Bendamustine, both in monotherapy and in combination regimens, is an effective therapy with a favorable toxicity profile in patients with indolent B-cell malignancies.

Liposomal cytarabine in advanced-stage acute lymphoblastic leukemia and aggressive lymphoma with central nervous system involvement : experience of The Polish Acute Leukemia Group

Department of Hematology and BMT, Silesian Medical University, Katowice, Department of Hematology, Institute of Hematology, Warsaw, Poland, Department of Hematology, Poznan Medical University, Poznan, Department of Hematology, Rzeszow Regional Hospital, Rzeszow, Department of Hematology and BMT, Medical University, Gdansk, Department of Hematology, Medical University, Lublin, and Department of Hematology, Medical University, Białystok, Poland

The importance of the number of transplanted cells with dipeptidyl peptidase-4 expression on the haematopoietic recovery and lymphocyte reconstitution in patients with multiple myeloma after autologous haematopoietic stem-cell transplantation

Autologous haematopoietic stem cell transplantation (AHSCT) remains recommended treatment in the first remission in multiple myeloma (MM). In earlier research it has been suggested that there is an influence of the expression of dipeptidyl peptidase‐4 (CD26) on both the homing and lymphocyte reconstitution after AHSCT. The aim of the study is to investigate the influence of transplanted cells CD26+ on the haematopoietic recovery and lymphocyte reconstitution after AHSCT in MM. Forty eight patients with MM underwent AHSCT in our centre. Number of all CD26+ cells, CD26+ lymphocytes, CD26+ monocytes and CD26+ and CD34+ cells were measured in the harvested material. Number of lymphocytes subpopulations (all lymphocytes CD3+, helpers, suppressors, natural killer (NK), cytotoxic NK and lymphocytes B) were measured in peripheral blood during regeneration after AHSCT. In both flow cytometry was used. On the basis of the analysis there was, as regards regeneration of haematopoietic cells after AHSCT, it was shown that a higher number of monocytes CD26+ improves the reconstitution of helper, suppressor and NK lymphocytes. A higher number of transplanted CD26+ lymphocytes accelerates the reconstitution of NK lymphocytes, whereas a higher number of all the cells CD26+ has a positive impact on the regeneration of cytotoxic NK lymphocytes. Copyright

Impact of granulocyte colony stimulating factor administered during induction and consolidation of adults with acute lymphoblastic leukemia on survival: long-term follow-up of the Polish adult leukemia group 4-96 study.

Department of Clinical Oncology, Comprehensive Cancer Centre, Maria Sklodowska-Curie Memorial Institute Branch Gliwice, Gliwice, Poland, Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland, Department of Hematology, Institute of Internal Diseases, Gdansk Medical Academy, Gdansk, Poland, Department of Hematology and Bone Marrow Transplantation, Lublin Medical Academy, Lublin, Poland, Department of Hematology, Oncology and Internal Medicine, Warsaw Medical University, Warsaw, Poland, Department of Hematology, Lodz Medical University, Lodz, Poland, Department of Internal Diseases, Institute of Haematology and Blood Transfusion, Warsaw, Poland, Department of Hematology, Institute of Haematology and Blood Transfusion, Warsaw, Poland, and Department of Hematology, Collegium Medicum, Jagiellonian University, Krakow, Poland

Could cytogenetics and minimal residual disease replace conventional risk criteria in adults with Ph-negative acute lymphoblastic leukaemia?

Novel immunoassay for the detection of hepatitis B surface ‘escape’ mutants and its application in liver transplant recipients. Journal of Medical Virology, 63, 210–216. Jongerius, J.M., Wester, M., Cuypers, H.T., van Oostendorp, W.R., Lelie, P.N., van der Poel, C.L. & van Leeuwen, E.F. (1998) New hepatitis B virus mutant form in a blood donor that is undetectable in several hepatitis B surface antigen screening assays. Transfusion, 38, 56–59. Lalazar, G., Rund, D. & Shouval, D. (2007) Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. British Journal of Haematology, 136, 699–712. Locarnini, S.A. (1998) Hepatitis B virus surface antigen and polymerase gene variants: potential virological and clinical significance. Hepatology, 27, 294–297. Marzano, A., Angelucci, E., Andreone, P., Brunetto, M., Bruno, R., Burra, P., Caraceni, P., Daniele, B., Di Marco, V., Fabrizi, F., Fagiuoli, S., Grossi, P., Lampertico, P., Meliconi, R., Mangia, A., Puoti, M., Raimondo, G. & Smedile, A. (2007) Prophylaxis and treatment of hepatitis B in immunocompromised patients. Digestive and Liver Disease, 39, 397–408. Moerman, B., Moons, V., Sommer, H., Schmitt, Y. & Stetter, M. (2004) Evaluation of sensitivity for wild type and mutant forms of hepatitis B surface antigen by four commercial HBsAg assays. Clinical Laboratory, 50, 159–162. Roque-Afonso, A.M., Ferey, M.P., Ly, T.D., Graube, A., Costa-Faria, L., Samuel, D. & Dussaix, E. (2007) Viral and clinical factors associated with surface gene variants among hepatitis B virus carriers. Antiviral Therapy, 12, 1255–1263.