Malgorzata Monika Trawinska

Severe peripheral arterial disease during nilotinib therapy

(36.4%) had a history of nicotine abuse, seven (63.6%) had arterial hypertension, three (27.3%) had diabetes mellitus, five (45.5%) had dyslipidemia, three (27.3%) were obese, six (54.5%) were male, and seven (63.6%) were older than 60 years (all cardiovascular risk factors). All 11 PAD patients had at least a cytogenetic remission while on nilotinib. One patient with hyper eosinophilic syndrome and one patient with CML received nilotinib as first-line treatment. Previous treatments for the remaining patients were hydroxyurea (nine patients), interferon alpha (seven patients), imatinib (nine patients), dasatinib (one patient), or another agent (four patients). In these 11 patients, the mean time from CML diagnosis to initiation of nilotinib was 347 weeks (range = 8–651 weeks) and the mean time from initiation of nilotinib to the first PAD event was 105.1 weeks (range = 16–212 weeks) (Table 1). In all cases, the lower limbs were affected; in nine patients, the femoral superficial artery was involved. These patients were treated with angioplasty (eight patients), stent implantation (eight patients), and/or amputation (four patients).

Characterization of Ph‐negative abnormal clones emerging during imatinib therapy

Imatinib is a tyrosine kinase‐specific inhibitor widely used for the treatment of chronic myeloid leukemia (CML). Studies reported the occurrence of additional cytogenetic abnormalities in the Philadelphia chromosome (Ph)‐negative cell population emerging after treatment‐induced suppression of the Ph‐positive clone. These abnormalities were described in a relatively high proportion of patients treated with imatinib compared with the anecdotal reports of similar cases in patients treated with other drugs. However, the origin of these abnormalities as well as their biological and clinical significance are unknown.

Transfusions at home in patients with myelodysplastic syndromes

We report descriptive data of a home care (HC) program, throughout a 5-years period (2006-2010), focusing on the reliability and the safety of transfusions at home in 211 patients affected by myelodysplastic syndromes (MDS). Our results outline the potentially relevant role of a specifically dedicated HC service in the global management of frail MDS patients for which transfusions at home may represent a valuable option to maintain a good quality of life and avoid the possible discomfort due to hospital admissions and outpatient visits.

Killer immunoglobulin-like receptors can predict TKI treatment-free remission in chronic myeloid leukemia patients

Several factors are predictive of treatment-free remission (TFR) in chronic myeloid leukemia (CML), but few data exist on the role of natural killer (NK) cells and their killer-cell immunoglobulin-like receptors (KIRs). KIR and human leukocyte antigen (HLA) genotypes were investigated in 36 CML patients who discontinued tyrosine kinase inhibitor (TKI) treatment after achieving deep molecular response (MR(4.5)). Cumulative TFR was significantly higher in patients homozygous for KIR A haplotype (85.7% vs. 45.5%; p = 0.029). Younger age, Bx haplotype, and the combination KIR3DS1/KIR3DL1 present/HLA-Bw4 present were significantly associated with relapse. KIR genotypes could prove useful in identifying patients that are likely to maintain MR(4.5) after discontinuing TKI treatment.

153Sm: its use in multiple myeloma and report of a clinical experience

Background: In the past years the bone seeking radiopharmaceutical samarium lexidronam (153Sm-EDTMP) has been increasingly used alone or in conjunction with chemotherapy and/or bisphosphonates for the treatment of painful bone metastasis. Objective: Its use has been explored in different solid tumours. In this report we explore its interesting characteristics and describe our experience in multiple myeloma (MM). Methods: 153Sm-EDTMP has an affinity for bone and concentrates in areas of bone turnover. It decays as a therapeutic β-emission and at the same time as γ-photon that can be used for tracking its concentration with bone scan imaging. Ten patients with symptomatic MM were treated to achieve pain control. Results: Encouraging results were obtained in MM patients. The use of this radioisotope could be largely improved.

Anticoagulant and Anti-thrombotic Treatments in the Management of Hematological Malignancies in a Home Care Program

Aim: Anticoagulants (AC) and anti-platelet (AP) agents are widely administered to patients with hematological malignancies (HM). However, HM patients may be at high risk of bleeding and hemorrhagic complications, because of different form of coagulopathies and several degrees of thrombocytopenia. Materials and Methods: A prospective evaluation of the use of anticoagulant and anti-thrombotic agents as well as of bleeding and thrombotic complications in a consecutive cohort of patients, which were followed during the first semester of 2010 by our home care service, was performed. In this regard, three pharmacological class of agents, such as oral anticoagulants (warfarin and acenocumarine), low molecular weight heparin (LMWH) and anti-platelet (AP) drugs were considered. Results: Out of 129 patients, 26 (20%) were treated with AC/AP drugs. Warfarin, acenocumarine, LMWH as well as AP were used in 7, 11 and 12 patients, respectively. Adverse events (bleeding) were observed in 3 patients (11.5%), 2 cases being on warfarin (replaced by LMWH) and 1 being AP (suspension without replacement); out of the 3 patients with bleeding, none presented thrombocytopenia. Conclusions: Despite the frequent findings of hemostatic disorders in a population of frail patients managed in a home care setting, our experience demonstrated that the use of AC/AP drugs has been very rarely responsible for significant complications.

Pyrrolo[1,2‐b][1,2,5]benzothiadiazepines (PBTDs) exert their anti‐proliferative activity by interfering with Akt–mTOR signaling and bax:bcl‐2 ratio modulation in cells from chronic myeloid leukemic patients

In our study we found that pyrrolo[1,2‐b][1,2,5]benzothiadiazepines (PBTDs) mediated apoptosis in primary leukemia cells from 27 chronic myelogenous leukemia (CML) patients at onset through the activation of the caspase‐9 and ‐3, and cleavage of poly (ADP‐ribose) polymerase (PARP). The bax:bcl‐2 ratio was increased as a consequence of down‐regulation of bcl‐2 and up‐regulation of bax proteins in response to treatment with PBTDs. In addition, PBTDs were able to induce cell death in primary leukemia cells derived from 23 CML‐chemoresistant patients. Furthermore, the effects of PBTDs on the Akt–mTOR (mammalian target of rapamycin) pathway were determined by Western blot. PBTDs possessed inhibitory activity against mTOR and also impeded hyper‐phosphorylation of Akt as a feedback of inhibition of mTOR by rapamycin. The results presented in this study demonstrate that we have identified the PBTDs as restoring the apoptotic pathways both in primary leukemia cells derived from CML patients at onset and in primary leukemia cells derived from CML‐chemoresistant patients, thus showing their ability to undergo apoptosis. These compounds constitute a promising therapeutic approach for patients with leukemia. They provide the basis for new strategies for an additional anticancer drug in leukemia therapies, especially when conventional ones fail. (Cancer Sci 2010; 101: 991–1000)

Frontline Dasatinib Treatment in a “Real-Life” Cohort of Patients Older than 65 Years with Chronic Myeloid Leukemia

Dasatinib (DAS) has been licensed for the frontline treatment in chronic myeloid leukemia (CML). However, very few data are available regarding its efficacy and toxicity in elderly patients with CML outside clinical trials. To address this issue, we set out a “real-life” cohort of 65 chronic phase CML patients older than 65 years (median age 75.1 years) treated frontline with DAS in 26 Italian centers from June 2012 to June 2015, focusing our attention on toxicity and efficacy data. One third of patients (20/65: 30.7%) had 3 or more comorbidities and required concomitant therapies; according to Sokal classification, 3 patients (4.6%) were low risk, 39 (60.0%) intermediate risk, and 20 (30.8%) high risk, whereas 3 (4.6%) were not classifiable. DAS starting dose was 100 mg once a day in 54 patients (83.0%), whereas 11 patients (17.0%) received less than 100 mg/day. Grade 3/4 hematologic and extrahematologic toxicities were reported in 8 (12.3%) and 12 (18.5%) patients, respectively. Overall, 10 patients (15.4%) permanently discontinued DAS because of toxicities. Pleural effusions (all WHO grades) occurred in 12 patients (18.5%) and in 5 of them occurred during the first 3 months. DAS treatment induced in 60/65 patients (92.3%) a complete cytogenetic response and in 50/65 (76.9%) also a major molecular response. These findings show that DAS might play an important role in the frontline treatment of CML patients >65 years old, proving efficacy and having a favorable safety profile also in elderly subjects with comorbidities.

Hammersmith score application identifies chronic myeloid leukemia patients with poor prognosis before treatment with second-generation tyrosine kinase inhibitors

In this study, we confirm the validity of the proposed Hammersmith score, which identifies three risk categories of patients and establish its strength on a large group of 128 chronic myeloid leukemia patients treated with second-generation tyrosine kinase inhibitors (TKIs) after being resistant to imatinib. Sixty-one patients were identified as good risk group, 27 patients as intermediate risk group, and 40 patients as poor risk group. The 1-year cumulative incidence of complete cytogenetic response was 73% in good risk patients, 40% in intermediate risk patients, and 22% in poor risk patients (P = 0.0001). Event-free survival at 3-year was 89% in good risk group, 70% in intermediate group, and 54% in poor risk group (P = 0.0001); the estimated 3-year progression-free survival was 95% in good risk category, 93% in intermediate risk category, and 87% in poor risk category (P=0.05). Kaplan-Meier estimated that the 3-year overall survival was 100% in good risk category, 93% in intermediate risk category, and 82% in poor risk category (P=0.04). In conclusion, some prognostic factors before starting second-generation TKIs might predict cytogenetic response and outcome. The so-called Hammersmith score was not yet validated in large series of patients: we demonstrated that this score is able to discriminate patients at high risk of failure and consequent progression before treatment with second-generation TKIs.

Long-lasting remission induced by rituximab in two cases of refractory autoimmune haemolytic anaemia due to cold agglutinins

Dear Sir, cold-agglutinin-induced autoimmune haemolytic anaemia (AIHA) can be a therapeutic challenge1, for which rituximab has been used with favourable results2–4. We report on two patients with refractory AIHA due to cold antibodies who were successfully treated with anti-CD20 monoclonal antibody in our institution.