"Secondary Chronic Myeloid Leukemia": Comparison between Patients Previously Exposed or Not to Chemo and/or Radiotherapy
Authors: Autore Francesco , Sora Federica , Chiusolo Patrizia , Annunziata Mario , Iurlo Alessandra , Cattaneo Daniele , Galimberti Sara , Bayer Jolanta , Leone Giuseppe , Sica Simona 
Published: October 2019

Abstract
Introduction. Haematological malignancies related to previous chemo and/or radio-therapy for neoplasia have been well investigated. This subgroup was defined as therapy-related myeloid neoplasms by ELN. In the field of chronic myeloid leukaemia (CML) the diagnosis of a secondary neoplasia after CML diagnosis has been studied but the presence of 'secondary CML' has not been completely defined. In clinical practice we collected patients with a CML diagnosis who had a previous history of malignancy.
Aim and methods. We reviewed our databases to collect the cases of 'secondary CML' in 4 hematological Italian centres.
Results. We found 51 patients who were diagnosed with previous malignancies out of 617 CML patients (8.3%). We conducted the analysis on 48 patients, removing the other three patients who were diagnosed before the era of tirosine-kinase inhibitors (TKIs). We then subdivided patients in two groups according to the treatment they received for the previous neoplasia: patients treated by surgery (group A: 27 patients) and patients treated by chemotherapy and/or radiotherapy (group B: 21 patients). Clinical characteristics at diagnosis of the patients of the two groups were summarized in Table 1.
The majority of the patients showed bcr-abl b3a2 (59% in group A and 62% in group B), no one showed additional cytogenetic abnormalities. The median time between the diagnosis of the primary neoplasia and CML were not different: 78 months (range 1-276) in the group A and 75 months (range 1-371) in the group B.
Upfront treatment was Imatinib in 55.6% of the patients in group A and 81% in group B; the remaining patients were treated with Dasatinib in 22.2% and 14% of the patients, respectively, and Nilotinib 22.2% and 5% of the patients, respectively.
All patients achieved haematological response after 1 month, 24 out of 27 patients (89%) of the group A achieved complete cytogenetic response after a median time of 3 months (range 3-28) and 20 out of 21 patients (95%) of the group B achieved complete cytogenetic response after a median time of 3 months (range 3-12). The median time of major molecular response was 9 months in 20 out of 27 patients (74%) of group A and in 19 out of 21 patients (90%) of group B.
Patients in group A showed a higher number of events who determined a change in the treatment: 9 patients (33.3%) in group A changed TKI due to resistance (3 patients: 2 primary resistance and 1 secondary resistance) or intolerance (6 patients) versus 4 patients (19%) of the group B because of resistance (3 patients: 2 primary resistance and 1 secondary resistance) or intolerance (1 patient). We recorded 3 deaths: 2 in the group A not related to CML and 1 in the group B due to CML. The median overall survival was 53 months (range 8-228) in the first group and 51 months (range 4-196) in the second group. Unexpectedly we found a 12.5% of patients with a previous diagnosis of lymphoma in patients developing CML and this reached statistical significance (p=0.004) when compared to patients in A group. We also detected 3 out of 48 CML patients (6%) with a previous history of 2 neoplasia and all of them were treated with chemo and/or radiotherapy.
Conclusion. Our research found that "secondary CML" occurred in 8.3% of newly diagnosed CML patients. Patients were comparable in terms of bcr-abl transcript, risk assessment, clinical and laboratory presentation. Cytogenetic and molecular response to TKIs as well as survival was similar to CML standard population. A significant fraction of patients with "secondary CML" received prior chemo and /or radiotherapy for an haematological malignancies and poses new questions in terms of either genetic predisposition and/or exposure to anticancer treatment.

Disclosures
No relevant conflicts of interest to declare.