Kazimierz Sulek

Cladribine, But Not Fludarabine, Added to Daunorubicin and Cytarabine During Induction Prolongs Survival of Patients With Acute Myeloid Leukemia: A Multicenter, Randomized Phase III Study

PURPOSE The goal of this study was to evaluate whether the addition of a purine analog, cladribine or fludarabine, to the standard induction regimen affects the outcome of adult patients with acute myeloid leukemia (AML). PATIENTS AND METHODS A cohort of 652 untreated AML patients with median age 47 years (range, 17 to 60 years) were randomly assigned to receive one of three induction regimens: DA (daunorubicin plus cytarabine), DAC (DA plus cladribine), or DAF (DA plus fludarabine). Postremission treatment was the same for all arms. RESULTS Complete remission rate in the DAC arm was higher compared with the DA arm (67.5% v 56%; P = .01) as a consequence of reduced incidence of resistant disease (21% v 34%; P = .004). There was no significant difference in early outcome between the DAF and DA arms. The probability of overall survival was improved for the DAC arm (45% ± 4% at 3 years) compared with the DA arm (33% ± 4%; P = .02), and leukemia-free survival was comparable. Long-term outcome did not differ significantly for the comparison of the DAF and DA arms. A survival advantage of the DAC arm over the DA arm was observed among patients age 50 years or older (P = .005), those with initial leukocyte count above 50 × 10(9)/L (P = .03), and those with unfavorable karyotype (P = .03). DAF revealed a significant advantage over DA in patients with adverse karyotype (P = .02). CONCLUSION The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.

Long-term results of the Polish Adult Leukemia Group PALG-CLL2 phase III randomized study comparing cladribine-based combinations in chronic lymphocytic leukemia

Abstract Long-term outcomes following newer therapies for chronic lymphocytic leukemia (CLL) have rarely been reported. This article presents the results of the final analysis of the Polish Adult Leukemia Group PALG-CLL2 study performed 10 years from final patient enrollment. With the extended follow-up time, it was found that cladribine (2-CdA)-based combinations CMC (2-CdA, cyclophosphamide, mitoxantrone) and CC (2-CdA, cyclophosphamide) administered as first-line treatment of progressive CLL resulted in significantly longer progression-free survival, but similar overall survival compared to 2-CdA monotherapy. Furthermore, the risk of potentially fatal late adverse events including infections, autoimmune complications and, particularly, secondary neoplasms was comparable among patients treated with CMC, CC or 2-CdA. The results of our analysis support the importance of long-term outcome monitoring of randomized trials in CLL.

Treatment of elderly patients with acute myeloid leukemia adjusted for performance status and presence of comorbidities: a Polish Adult Leukemia Group study

This prospective study estimated outcomes in 509 elderly patients with acute myeloid leukemia (AML) with different treatment approaches depending on Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI). Patients were stratified into fit (ECOG 0–2 and CCI 0–2) or frail (ECOG > 2 and/or CCI > 2) groups. Fit patients with CCI 0 received intensive chemotherapy whilst reduced-intensive chemotherapy (R-IC) was given to those with CCI 1–2. Frail patients received best supportive therapy. Fit patients presented a longer overall survival (OS) than frail subjects, but 8-week mortality rates were similar. The complete response (CR) rate between fit CCI 0 and CCI 1–2 subgroups was significantly different. Both of the fit subgroups showed similar 8-week mortality rates and OS probabilities. Allocating fit patients with CCI 1–2 to R-IC enabled an increase in the group of elderly patients who could be treated with the intention of inducing remission.

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study

The importance of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo‐HSCT. These consisted of leukemia‐free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non‐relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999–2008. The Mantel–Byar approach was used to assess allo‐HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo‐HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41–60. The CIR demonstrated that allo‐HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo‐HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41–60. The allo‐HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. Am. J. Hematol. 90:904–909, 2015.

Immune thrombocytopenia in patients with chronic lymphocytic leukemia treated with cladribine-based regiments or chlorambucil – follow-up of PALG-CLL randomized trials

The relationship between treatments of chronic lymphocytic leukemia (CLL) with cladribine (2‐CdA) or chlorambucil and immune thrombocytopenia (IT) has not been yet determined.

Clinical and morphological practices in the diagnosis of transplant-associated microangiopathy: a study on behalf of Transplant Complications Working Party of the EBMT

Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). This study evaluated clinical and morphological practices of TA-TMA diagnosis in EBMT centers. Two questionnaires, one for transplant physician and one for morphologist, and also a set of electronic blood slides from 10 patients with TA-TMA and 10 control patients with various erythrocyte abnormalities, were implemented for evaluation. Seventeen EBMT centers participated in the study. Regarding criteria used for TA-TMA diagnosis, centers reported as follows: 41% of centers used the International Working Group (IWG) criteria, 41% used “overall TA-TMA” criteria and 18% used physician’s decision. The threshold of schistocytes to establish TA-TMA diagnosis in the participating centers was significantly associated with morphological results of test cases evaluations (p = 0.002). The mean number of schistocytes reported from blood slide analyses were 4.3 ± 4.5% for TA-TMA cases (range 0–19.6%, coefficient of variation (CV) 0.7) and 1.3 ± 1.6% for control cases (range 0–8.3%, CV 0.8). Half of the centers reported schistocyte levels below 4% for 7/10 TA-TMA cases. The intracenter variability was low, indicating differences in the institutional practices of morphological evaluation. In conclusion, the survey identified the need for the standardization of TA-TMA morphological diagnosis.

Value of the NBT test in the diagnosis of bacterial infection in untreated cancer patients and in those on radio- and/or chemotherapy.

As the first step in the study, the results of the NBT test in 83 patients with various untreated neoplasms, including 20 lymphomas, without bacterial infections and in 35 neoplastic patients with this complications were compared with the results obtained in control groups. No significant differences in the results were found between the groups of neoplastic patients without or with bacterial infections and the controls. To evaluate the NBT test during radio- and/or chemotherapy, especially in neutropenia, 45 patients were NBT-monitored. During the study of 102 episodes of neutropenia 43 infections occurred and 30 were NBT-confirmed. In remaining 13 cases it was impossible to perform the test because of extremely low neutrophil count (below 500/mul). All 20 infections in patients with normal neutrophil count were NBT-positive. These results confirm the usefulness of the test for infection screening in untreated with malignancies, as well as in patients receiving radio- and/or chemotherapy. However, the test can be taken only in patients without severe neutropenia.