• PALG AML 1999 (DAC vs. DA) Study - phase III, multicenter, central randomized, comparison of DAC (daunorubicin, cytarabine, cladribine), and standard DA (daunorubicin, cytarabine) regimen as a induction therapy in untreated AML patients in age 18 - 60. 
  Publication: Hołowiecki J, Grosicki S, Robak T, Krzemień S, Hellmann A, Skotnicki A, Jędrzejczak W, Giebel S, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Mariańska B, Pluta A, Zawilska K, Komarnicki M, Kłoczko J, Haus O, Stella-Hołowiecka B et al.: Addition of 2-CdA to daunorubicin and cytarabine results in higher CR rate after a single cours of induction treatment in AML and improves outcome in patients with adverse prognostic factors. A randomized, multicenter phase III study. Leukemia. 2004 May;18(5):989-97.

  Five years follow up was presented during Annual ASH Meeting 2004 in San Diego

  Addition of Cladribine to the Standard AML Treatment Improves Long-Term Outcome in High Tumor Burden and Older Than 40 Years Acute Myeloid Leukemia Patients. Five-Year Follow-Up of the Polish Adult Leukemia Group (PALG 1999 DAC vs. DA Study). Session Type: Poster Session 8-II Jerzy Holowiecki, Sebastian Grosicki, Tadeusz Robak, Slawomira Krzemien, Sebastian Giebel, Andrzej Hellmann, Aleksander Skotnicki, Wieslaw W. Jedrzejczak, Lech Konopka, Kazimierz Kuliczkowski, Barbara Zdziarska, Anna Dmoszynska Poster Session: Adult and Pediatric AML - Novel Agents and Immunotherapy.

   

• PALG AML Study in Elderly Patients (> 60 yrs) - phase II, multicenter, central randomised,; comparison of mitoxantrone + etoposide + LD cytarabine with standard 3+7 (daunorubicine + cytarabine) as induction therapy in > 60 yrs patients. Publication: Wierzbowska A., Wrzesień-Kuś A., Robak T., Jamroziak K., Lech-Marańda E., Hołowiecki J., Krzemień S., Kuliczkowski K., Mazur G., Jędrzejczak W.W., Mądry K., Kłoczko J., Piszcz J., Dmoszyńska A., Adamczyk-Cioch M., Maj S., Mariańska B., Konopka L., Hellmann A., Całbecka M.: Porównanie wyników leczenia ostrej białaczki szpikowej (OBS) mitoxantronem, etopozydem, małymi dawkami cytarabiny ze standardową chemioterapią daunorubicyną z cytozarem (3+7) u chorych powyżej 60 r.ż. Randomizowane badanie kliniczne II Fazy Polskiej Grupy Badawczej d.s. Białaczek (PALG). Acta Haematologica Polonica 2003, 34, 1, 73-84.

• PALG AML 1999 DAC Study - phase II; multicenter program; assessment of the toxicity and efficacy of DAC (daunorubicin, cytarabine, cladribine) protocol in patients with primary resistant or relapsed acute myeloid leukemia in age 18-65. Publication: Hołowiecki J., Robak T., Kyrcz-Krzemień S., Grosicki S., Wrzesień-Kuś A., Hellmann A., Skotnicki A., Jędrzejczak W., Konopka L., Zdziarska B.: Daunorubicin, cytarabine and 2-CdA (DAC-7) for remission induction in "de novo" adult acute myeloid leukaemia patients. Evaluation of safety, tolerance and antileukemic activity. Acta Haematologica Polonica 2002, 33, 2, 239-247

  
  

 - Acute lymphoblastic leukemia  

Ongoing studies

1. Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult ALL - a phase II study.
   In this clinical phase II study a novel protocol consisted of fludarabine, cyterabine, and mitoxantrone (FLAM) was evaluated in adult ALL patients who fail to achieve CR after one or more courses of induction therapy, those who relapse early (<6 months) after achieving CR, and those who relapse after HCT regardless the remission duration. Among 51 patients analysed, the CR rate was 46%. The regimen required intense supportive therapy, however fatal events were restricted mainly to patients aged>40 years. It seems that FLAM is particularily effective for T-lineage ALL. It may serve to induce reduce tumour burden before high dose therapy followed by alloHCT. The interim analysis was presented during the ASH 2003 meeting in San Diego (Blood 2003, 102, 11, 3286, 883a). The final analysis is currently being prepared for publication.

2. Prognostic value of minimal residual disease monitored with the use of immunophenotyping, for long-term outcome of acute lymphoblastic leukaemia in adults; a prospective, multicentre study of the Polish Adult Leukaemia Group.
   The goal of this study is to analyse prognostic value of the detection of minimal residual disease (MRD), with the use of immunophenotyping, for long-term outcome of acute lymphoblastic leukaemia in adults. Two hundred patients treated in 15 centres belonging to Polish Adult Leukaemia Group (PALG) will be included within three years. The therapy will be conducted according to the current PALG 4-2002 protocol, including pre-treatment (prednisolone), induction (epirubicin, vincristin, prednisolone, asparaginase), and consolidation (cytarabine, cyclophosphamide, methotrexate, mercaptopurine, etoposide, CNS irradiation). Before start of the treatment, immunophenotype of leukaemic blasts will be established and will further serve for MRD detection with the use of "quadrants" and "empty spaces" methods. The final analysis will focus on the influence of the presence of MRD detected at the level of 1/103 marrow cells, examined after induction and after consolidation phase in patients being in complete haematological remission, on the 5-years probability of relapse. Secondary goal of the study is to determine the expression of CD20 and CD52 antigens on acute lymphoblastic leukaemia cells. These antigens may be targets for immunotherapy with the use of monoclonal antibodies. The recruitment started in January 2004 and is ongoing.

3. Open-label, multicentre study to evaluate imatinib as part of the maintenance therapy of adult bcr/abl - positive ALL patients.
   In this study 70 bcr/abl (positive) adult ALL patients who are not eligible for allogeneic transplantation, will be included after conclusion of intense induction-consolidation therapy. Patients will be traeted with imatinib and mercaptopurine/metotrexate in time-sequenced fashion as the maintenance treatment. In course of the treatment patients may additionally be performed autologous HCT procedure. The recruitment will start at the end of 2004 and is planned for 2 years. Long-term outcome of the patients will be evaluated and compared with the historical control derived from the PALG database.
   

Published studies

1. G-CSF administered in time-sequenced setting during remission induction and consolidation therapy of adult acute lymphoblastic leukemia; a randomized multicentre PALG 4-96 study. (Leukemia & Lymphoma, 2002, 43, 315-325)
   

   The goal of this randomized, multicentre study conducted between 1997-1998 was to evaluate G-CSF (lenograstim) administered during the induction and consolidation treatment of adult ALL patients. Based on previous experimental and clinical experience, the cytokine was given in time-sequenced settings i.e. started 36 hours after epirubicine infusion and discontinued 48 hours before the next dose. This mode of administration was believed to protect normal hematopoiesis. We proved that time-sequenced G-CSF resulted in shorter neutrophil recovery after induction and consolidation and enabled better adherence to the therapy protocol. In the early evaluation more intense therapy seemed to result in improved the overall survival.

   Four-year follow-up analysis confirmed the trend and was presented during the EHA 2000 meeting in Florence (The Haematology Journal 2000, 1, Suppl. 1, 23). The most recent follow-up of the study was presented during the ASH 2004 meeting in San Diego (Blood 2004, 104, 747a).

2. Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG) experience. (Ann Hematol. 2004 Apr; 83(4):225-31)
   Retrospective, multicenter study to evaluate biological features and outcome of elderly patients diagnosed with acute lymphoblastic leukemia (ALL) during the last 10 years in ten hematological centers in Poland.