Irene Zacheo

Dasatinib combined with weekly administration of vincristine as effective therapy in sudden or resistant Ph+ lymphoid blast crisis of chronic myeloid leukaemia

Blood, 115, 2619–2629. Lee, B.N., Gao, H., Cohen, E.N., Badoux, X., Wierda, W.G., Estrov, Z., Faderl, S.H., Keating, M.J., Ferrajoli, A. & Reuben, J.M. (2011) Treatment with lenalidomide modulates T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia. Cancer, 117, 3999–4008. Lundin, J., Porwit-MacDonald, A., Rossmann, E. D., Karlsson, C., Edman, P., Rezvany, M.R., Kimby, E., Osterborg, A. & Mellstedt, H. (2004) Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia. Leukemia, 18, 484–490. Osterborg, A., Karlsson, C., Lundin, J., Kimby, E. & Mellstedt, H. (2006) Strategies in the management of alemtuzumab-related side effects. Seminars in Oncology, 33, S29–S35.

Correlation between Charlson comorbidity index and outcome in patients with chronic phase chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors upfront

In chronic myeloid leukemia (CML) the presence of comorbidities has gained importance because, following the availability of different drugs, it has become paramount to choose the correct drug base...

Long-term outcome of chronic myeloid leukaemia patients with p210 and p190 co-expression at baseline

186–197. Pongers-Willemse, M.J., Verhagen, O.J., Tibbe, G.J., Wijkhuijs, A.J., de Haas, V., Roovers, E., van der Schoot, C.E. & van Dongen, J.J. (1998) Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia, 12, 2006–2014. Pott, C. (2011) Minimal residual disease detection in mantle cell lymphoma: technical aspects and clinical relevance. Seminars in Hematology, 48, 172–184. Pott, C., Hoster, E., Delfau-Larue, M.H., Beldjord, K., Bottcher, S., Asnafi, V., Plonquet, A., Siebert, R., Callet-Bauchu, E., Andersen, N., van Dongen, J.J., Klapper, W., Berger, F., Ribrag, V., van Hoof, A.L., Trneny, M., Walewski, J., Dreger, P., Unterhalt, M., Hiddemann, W., Kneba, M., Kluin-Nelemans, H.C., Hermine, O., Macintyre, E. & Dreyling, M. (2010) Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood, 115, 3215–3223. Pott, C., Bruggemann, M., Ritgen, M., van der Velden, V.H., van Dongen, J.J. & Kneba, M. (2013) MRD detection in B-cell non-Hodgkin lymphomas using Ig gene rearrangements and chromosomal translocations as targets for realtime quantitative PCR. Methods in Molecular Biology, 971, 175–200. van der Velden, V.H., Cazzaniga, G., Schrauder, A., Hancock, J., Bader, P., Panzer-Grumayer, E.R., Flohr, T., Sutton, R., Cave, H., Madsen, H.O., Cayuela, J.M., Trka, J., Eckert, C., Foroni, L., Zur Stadt, U., Beldjord, K., Raff, T., van der Schoot, C.E. & van Dongen, J.J. European Study Group on, M.R.D.d.i.A.L.L. (2007) Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia, 21, 604–611. Verhagen, O.J., Willemse, M.J., Breunis, W.B., Wijkhuijs, A.J., Jacobs, D.C., Joosten, S.A., van Wering, E.R., van Dongen, J.J. & van der Schoot, C.E. (2000) Application of germline IGH probes in real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia. Leukemia, 14, 1426–1435.

Azacitidine for myelodysplastic patients aged > 65 years: a review of clinical efficacy

Introduction: Therapeutic strategies for elderly patients affected by myelodysplastic syndromes (MDS) are scarce and only few patients have an advantage in performing allogeneic bone marrow transplant. Areas covered: Primary endpoints for treatment of elderly MDS patients were not curative, but rather allowing to maintain a good quality of life through prolongation of overall survival. In this context, azacitidine showed to improve responses in this subset of patients compared to conventional established regimens, such as intensive or low-dose chemotherapy and best supportive care. Good safety profile of the drug was reported either when it was used inside or outside clinical trials. Improved quality of response was observed when the drug was administered beyond the first response, and it is now usually recommended to continue it at the same dose and schedule in responding patients. Expert opinion: Evaluation of baseline prognostic factors and comorbidities may help to identify patients who can benefit from the prolonged administration of the drug. Real life data regarding efficacy and safety of azacitidine in MDS elderly patients are required in order to confirm the results of clinical trials.

Combination of azacitidine and ESA in myelodysplastic patients: the need for prospective studies.

We read with great interest the paper by Itzkynson et al. [1] hat reported the results of the combination of erythropoietin and zacitidine in myelodysplastic syndrome (MDS) patients. Overall, 2 out of 282 patients were treated concomitantly with azacitiine and erythropoietic stimulating agents (ESA) for a relatively hort period of time (median duration 5.8 months). The authors eported an overall response rate of 53% in patients treated with the ombination compared to 43% in patients treated with azacitidine lone, without statistically significant difference. No differences ere reported in terms of complete response (CR) and marrow esponse (mCR) between the two groups of subjects, whereas the ate of hematologic improvement-erythroid (HI-E) was superior in he combination group (44%) compared to azacitidine alone group 27%), with an increased rate of patients becoming transfusion ndependent in the former group. Again no difference in terms of rogression rate was observed, whereas ESA-treated patients had longer survival (OS), with a median of 19.6 months compared to 1.9 months for patients who did not receive ESA. With the aim to valuate the possible effect of the above described combination, 60 DS patients treated with azacitidine in our institute, 8 of whom eceived the drug in association with ESA, were retrospectively anaysed. There were 44 males and 16 females, median age 69 years range 44–83). According to WHO criteria [2], 35 patients were

Incidence of persistent/late chronic anemia in newly diagnosed patients with chronic myeloid leukemia responsive to imatinib

In patients with chronic myeloid leukemia (CML) responsive to imatinib, it is still unknown whether the long‐lasting treatment could induce the appearance of a persistent/late chronic anemia. To highlight this issue, we revised 128 patients with CML (M/F 64/64, median age at diagnosis 56.9 years, interquartile range 43.0–69.3) treated at our Institution with 1st line imatinib for at least 36 months and in stable complete cytogenetic response. At the 36th month of imatinib, a chronic anemia (Hb < 12 g/dl for > 6 months) was present in 38/128 patients (29.6%): the anemia was moderate (Hb > 8 ≤ 10 g/dl) in 12 patients (9.3%) and mild (Hb > 10 < 12 g/dl) in 26 patients (20.3%). All patients with persistent/late chronic anemia had a low reticulocyte count and 8/38 a condition of iron deficiency without clinical and instrumental signs of chronic blood loss. Four out of 38 patients (10.5%) needed red cell transfusions during the follow‐up. At a landmark analysis from the 36th month of imatinib treatment, cumulative 4‐year overall survival (OS) for patients with chronic anemia was 94.4% (CI 95% 83.8–100) compared to 93.5% (CI 95% 87.2–99.8) for patients without chronic anemia (P = 0.617). In conclusion, the occurrence of a late chronic anemia during long‐lasting treatment with imatinib has been observed in about 30% of our responsive patients: its occurrence does not seem to affect OS, but its real impact should be evaluated on a larger cohort of patients. Am. J. Hematol. 90:105–108, 2015.

Application of comorbidity indexes at baseline could be useful to predict rates of response in patients with chronic myeloid leukemia treated with imatinib

In patients with cancer, comorbidities and poor performance status generally infl uence prognosis and aff ect therapeutic plans and outcome. In particular, comorbidities may have an impact on survival and choice of treatment among patients with cancer; comorbidities have been identifi ed as signifi cant determinants of response to therapy in older patients with acute myeloid leukemia, or female breast cancer, or head and neck or lung cancer [1]. Recently, we evaluated the impact of comorbidities in a large series of elderly patients with chronic myeloid leukemia (CML) treated with dasatinib after imatinib failure, with the aim of establishing associations between comorbidities and the development of pleural eff usions or compliance to the drug [2]. Th e prognostic importance of comorbidities in CML has never been evaluated in relation to active treatment. Th e aim of the present study was to compare and validate three diff erent non-specifi c comorbidity scores (Charlson Comorbidity Index [CCI] [3], Cumulative Illness Rating Scale [CIRS] [4] and Adult Comorbidity Evaluation 27 [ACE-27] [5]) by applying them to a cohort of patients with CML treated with imatinib as fi rst or second line after interferon (IFN) failure. All patients entered in this study were diagnosed and followed between 1995 and 2010 at the Sapienza University of Rome, outside of clinical trials. In all cases, diagnosis was confi rmed at the cytogenetics (conventional banding analysis, CBA) and the molecular level (reverse trancriptase [RT]- and real-time quantitative polymerase chain reaction [RQ-PCR] for identifi cation of Philadelphia chromosome positivity (Ph ) and BCR/ABL1 transcript). Of 343 patients enrolled in this study, 142 fi rst received interferon- α outside of clinical trials and were then switched to imatinib for failure; for this group of patients, data relating to comorbidities were collected at the time of the start of imatinib. Th e remaining 201 patients were treated consecutively with imatinib as fi rst line from January 2000 onward. Risk evaluation at baseline was performed using the Sokal score, and retrospectively with the European Treatment and Outcome Study (EUTOS) score. All patients were followed according to European LeukemiaNet (ELN) guidelines from 2006 to date [6]. Cytogenetics analysis was performed after 3 months from the start and then at 6 and 12 months, and then every year after a complete cytogenetic response (CCyR) was achieved. Results were expressed according to ELN defi nitions, according to CBA fi ndings. Molecular testing was performed with RQ-PCR every 3 months using peripheral blood, and then every 6 months after a major molecular response (MMR) or a complete molecular response (CMR) was achieved. Results were expressed as a ratio relative to an ABL1 control, with the fi nal value converted to the International Scale (IS). We considered as primary resistance the lack of any cytogenetic response, whereas secondary resistance was the achievement and subsequent loss of cytogenetic or molecular response. Application of the CCI revealed that 182 patients had score 0 – 2 (50%), 101 patients had score 3 (29%), 47 patients had score 4 (13.7%) and 13 patients had score 5 (3.7%). We found a signifi cant correlation between stratifi cation according to the CCI and cumulative incidence of CCyR ( p 0.02, Figure 1), cumulative incidence of MMR ( p 0.03) and cumulative incidence of primary and secondary resistance ( p 0.01, Table I). Application of the ACE-27 index in 338 evaluable patients identifi ed 170 patients (50%) as having score 2 and 168 patients (49.7%) as having score 3; we did not reveal any substantial diff erence according to this stratifi cation in terms of CCyR, MMR or resistance (Table I). Finally, we applied the CIRS score in 334 patients, which identifi ed 155 patients as having score 1 (46%), 96 patients as having score 2 (29%), 61 patients as having score 3 (18%), 20 patients as having score 4 (6%) and two patients as having score 6 (0.6%). Again, as for the ACE-27 index, we did not fi nd any signifi cant association between CIRS stratifi cation and cumulative incidences of CCyR, MMR and resistance. We compared imatinib dose intensity, temporary dose interruption and permanent discontinuation according to the CCI. We found a signifi cant correlation between higher scores of the CCI and low compliance to treatment due to the higher rate of toxicity and consequently higher rate of temporary (21% in patients with score 0 – 2 vs. 56% in patients with score 3, p 0.01) and permanent discontinuation (5%