Case report: Pleural effusion during tyrosine-kinase inhibitor treatment in chronic myeloid leukemia: Not only a dasatinib-related adverse event.

The spectrum of TKI-related adverse events (AEs) is variable. Pleural effusion (PE) is a frequent AE attributable to dasatinib treatment, while it is only rarely associated with nilotinib. The pathogenetic mechanism leading to PE during nilotinib therapy is still unknown and its management has not yet been defined. To the best of our knowledge, only a limited number of similar case reports have already been reported in the literature so far. Here, we describe the case of a 41-year-old CML patient who developed PE during first-line nilotinib, successfully treated with steroids and nilotinib permanent discontinuation. We highlight the differences among our patient and the others, proposing therapeutic strategies to solve this rare but still possible AE, of which physicians should be aware.

Ponatinib as a Valid Alternative Strategy in Patients with Blast Crisis-Chronic Myeloid Leukemia Not Eligible for Allogeneic Stem Cells Transplantation and/or Conventional Chemotherapy: Report of a Case.

Currently, imatinib and dasatinib are the only tyrosine-kinase inhibitors approved in the US and Europe for the treatment of blast crisis of chronic myeloid leukemia (BC-CML) at diagnosis, while ponatinib is the only inhibitor used in patients bearing T315I mutation. Here we report the case of a 61-year-old man diagnosed with B-cell lymphoid BC-CML, initially treated with imatinib 800 mg day and then with dasatinib 140 mg day because of intolerance. A complete cytogenetic response (CCyR) was achieved at three months; however, three months later a relapse was observed, and the T315I mutation was detected. Ponatinib 45 mg once daily was then started together with a short course of chemotherapy. Bone marrow evaluation after six months of therapy showed the regaining of CCyR, together with the achievement of a deep molecular response. However, one year from ponatinib start the patient experienced a new disease relapse; he was effectively treated with ponatinib and chemotherapy once again, but in the meanwhile an ischemic stroke was detected. This case report confirms the high efficacy of ponatinib monotherapy in BC-CML patients, representing a valid option for non-allogeneic stem cells transplantation eligible cases and the only one available for those carrying the T315I mutation.

Comprehensive Molecular Analyses in a Case of Masked Philadelphia Chronic Myeloid Leukemia.

Here, we report the case of an 80-year-old woman with masked Philadelphia chronic myeloid leukemia (Ph CML). At diagnosis, qualitative PCR demonstrated the presence of a typical e14a2 configuration, and chromosome analysis showed an apparently normal female karyotype. However, FISH with BCR-ABL1 dual fusion probes gave a positive signal in 152/200 analyzed nuclei, with the fusion signal detected on the long arm of a cytogenetically normal chromosome 9. Using locus-specific probes for chromosome 9 and 22 telomeres, a third chromosome involvement was excluded. Furthermore, microarray analysis from the same specimens showed a normal result. Due to a high Charlson Comorbidity Index, the patient was treated with a reduced dose of imatinib, achieving a rapid hematological response after 1 month. However, after 6 months of imatinib therapy, she had to be considered as warning (Ph+ 26.5%, BCR-ABL1 >1%) according to the European LeukemiaNet 2013 recommendations. In conclusion, we confirmed the importance of a combination of cytogenetic and molecular techniques for the diagnosis and therapy monitoring of masked Ph CML, but, different from what has been reported in the literature so far, we cannot completely exclude the fact that the unusual cytogenetic pattern of this patient may have negatively influenced her response to tyrosine kinase inhibitor therapy.

Comorbidities and polypharmacy impact on complete cytogenetic response in chronic myeloid leukaemia elderly patients.

BACKGROUND: In older patients comorbidity and polypharmacy can significantly influence the success of the treatment, as well as the cognitive and psycho-social aspects. A significant proportion of chronic myeloid leukaemia (CML) patients are "elderly": in the past the aim of therapy in this subset of patients was only to contain the leukaemic mass, but nowadays, with the advent of the protein-tyrosine kinase inhibitors, also elderly patients can access these treatments. We want to assess if even old CML patients, with a correct geriatric evaluation, can be successfully treated with protein-tyrosine kinase inhibitors. METHODS: A complete geriatric evaluation in 16 old CML patients aged >65years treated with TKI was performed in order to assess the comorbidity, the polypharmacy and the cognitive, physical and psychological states. The Charlson comorbity index (CCI) and the polypharmacy were correlated to the obtained cytogenetic response. Seven scales of geriatric evaluation were used to assess the autonomy of patients before they were included into the study. RESULTS: In our cohort of elderly patients treated with imatinib, comorbidities and polypharmaco-therapy demonstrated an influence on TKI therapeutic success. In fact, the majority of complete cytogenetic response was obtained by patients who presented a low score of CCI and did not take any other drugs other than TKI. CONCLUSION: Also old chronic myeloid leukaemia patients can benefit from TKI treatment if a good cooperation between the haematologist and the geriatrician is established.

Cellular properties of human erythrocytes preserved in saline-adenine-glucose-mannitol in the presence of L-carnitine.

L-Carnitine (LC) in the preservation medium during storage of red blood cells (RBC) can improve the mean 24-hr percent recovery in vivo and increase RBC life-span after reinfusion. The purpose of the study was to investigate the differences in the biochemical properties of RBCs stored in the presence or absence of LC, and the cell-age related responses to storage conditions and to LC. RBC concentrates in saline-adenine-glucose-mannitol (SAG-M) were stored in the presence or absence of 5 mM LC at 4 degrees C for up to 8 weeks. RBC subpopulations of different densities were prepared by centrifugation on Stractan density gradient. Cells were sampled at 0, 3, 6, and 8 weeks, and hematological and cellular properties analyzed (MCV, MCHC, 4.1a/4.1b ratio as a cell age parameter, intracellular Na(+) and K(+)). After 6 weeks, MCV of RBC stored in the presence of LC was lower than that of controls (6 weeks MCV: controls 95.4 +/- 1.8 fl; LC 91.5 +/- 2.0 fl; n = 6; P < 0.005). This was due to swelling of control cells, and affected mainly older RBCs. LC appeared to reduce or retard cell swelling. Among the osmotically active substances whose changes during storage could contribute to cell swelling, only intracellular Na(+) and K(+) differed between stored control RBCs and LC-treated cells. LC reduces the swelling of older cells during storage at 4 degrees C in SAG-M, possibly by acting on the permeability of cell membrane to monovalent cations.