Ida Carmosino

Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features

Although the occurrence of thrombosis in acute promyelocytic leukemia (APL) has been reported during retinoic acid treatment, no studies carried out in large clinical cohorts have specifically addressed this issue. We analyzed 124 APL patients treated with the all-trans retinoic acid and idarubicin protocol and compared clinico-biologic characteristics of 11 patients who developed thrombosis with those of 113 patients who had no thrombosis. In seven patients, the events were recorded during induction, whereas in four patients deep vein thrombosis occurred in the post-induction phase. Comparison of clinico-biological characteristics of patients with and without thrombosis revealed in the former group higher median white blood cell (WBC) count (17 × 109/l, range 1.2–56, P=0.002), prevalence of the bcr3 transcript type (72 vs 48%, P=0.01), of FLT3-ITD (64 vs 28%, P=0.02), CD2 (P=0.0001) and CD15 (P=0.01) expression. No correlation was found with sex, age, French-American-British subtype, all-trans-retinoic acid syndrome or with thrombophilic state that was investigated in 5/11 patients. Our findings suggest that, in APL patients consistent biologic features of leukemia cells may predict increased risk of developing thrombosis.

Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib

Abstract:  Imatinib related non‐haematological side‐effects are reported in <10% of chronic myeloid leukaemia patients and include oedema, weight gain, nausea, vomiting and muscle cramps. Cutaneous reactions are well‐recognized events occurring mostly in patients treated at doses of 600 mg/d and higher, either in stable or progressive disease. We report on our experience relating to dermatological toxicities in imatinib treated CML patients showing a spectrum of skin reactions ranging from rashes to cutaneous carcinoma.

Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians

Background The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia. Design and Methods From February 2003 to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E). Results Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected [median QOL-E standardized score 54, interquartile range 46–70; median EORTC global score 50, interquartile range 41–66]. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients’ perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores. Conclusions Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.

Early detection of meningeal localization in acute promyelocytic leukaemia patients with high presenting leucocyte count

Summary. Extramedullary relapse occurs infrequently in acute promyelocytic leukaemia (APL) but has been increasingly reported after the advent of all‐trans retinoic acid (ATRA) treatment, probably as a consequence of improved patient survival. We describe our single centre experience of six APL patients who had disease localization in the central nervous system (CNS). In three patients, clinical symptoms (headache and/or nausea) that presented during follow‐up led to the performance of a lumbar puncture and detection of overt CNS infiltration. Two of these patients had simultaneous haematological relapse and one was in molecular remission when CNS leukaemia was documented. One patient with no local symptoms showed CNS infiltration at the time of molecular relapse. Following the introduction of routine lumbar puncture, carried out after front‐line induction in all newly diagnosed patients with white blood cell count (WBC) greater than 10 × 109/l, two additional patients in molecular remission with no local symptoms were found to have initial APL localization in the CNS. Presenting features included in 6/6 patients an elevated WBC count (> 10 × 109/l) and a predominance of the PML/RAR bcr3 type (5/6 patients) and of microgranular morphology (5/6 patients). Our findings highlight the importance of carrying out lumbar puncture in APL patients presenting with high‐risk features.

Darbepoetin alfa for the treatment of anemia associated with myelodysplastic syndromes: efficacy and quality of life.

To evaluate efficacy, safety, changes in biological features, and quality of life (QoL) in low-risk anemic patients with MDS treated with darbepoetin alfa (DPO), 41 patients received DPO 150 μg weekly for 24 weeks. The dose was increased to 300 μg weekly in non-responsive patients. During treatment, 10/17 (59%) transfusion-dependent (TD) and 13/23 (56%) transfusion-free (TF) patients responded. In TF patients, Hb increased from 9.2 ± 0.9 g/dL to 10.3 ± 1.4 g/dL by 24 weeks (p = 0.004). The mean response duration was 22 weeks (95% CI: 19.7–24.0) in TF patients compared with 15.1 weeks (95% CI: 13.3–17.5) in TD patients. Response to treatment was associated with increases in QoL. Decreases in the percentage of apoptotic progenitor cells (p = 0.007) and CD34+ cells (p = 0.005) were observed. These results confirm previous studies demonstrating the safety and efficacy of DPO in anemic patients with MDS. Biological changes and improvement in QoL were associated with response. Adequate dosing is to be determined.

Reactivation of porphyria cutanea tarda as a possible side effect of Imatinib at high dosage in chronic myeloid leukemia

Reactivation of porphyria cutanea tarda as a possible side effect of Imatinib at high dosage in chronic myeloid leukemia

Sudden Blast Crisis in Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Achieved Complete Cytogenetic Remission After Imatinib Therapy

Most patients with Philadelphia chromosome (Ph)‐positive chronic myeloid leukemia (CML) in chronic phase (CP) who receive treatment with imatinib achieve complete cytogenetic remission (CCR), which is correlated tightly with long‐term progression‐free survival. In these patients, the occurrence of blastic crisis (BC) is rare, and its clinical biologic characteristics are not well known.

Ogilvie's syndrome in acute myeloid leukemia: pharmacological approach with neostigmine

Abstract. Acute colonic pseudo-obstruction, the so-called Ogilvies syndrome, is a rare and life-threatening digestive complication usually observed in critically ill patients. It is characterized by signs of large-bowel obstruction, without a mechanical cause, and has been reported in various settings, including acute leukemias as a complication of neutropenic enterocolitis after intensive chemotherapy. We describe the case of a young woman who, during the neutropenic phase following autologous bone marrow transplantation for relapsed acute myeloid leukemia, developed neutropenic enterocolitis complicated by an acute pseudo-obstruction of descendent colon and sigma. This process was associated with sepsis and resolved with conservative therapy of the underlying condition, using granulocyte colony-stimulating factor and intravenous neostigmine. We discuss the management of this rare syndrome.

Treatment of long-lasting priapism in chronic myeloid leukemia at onset

Priapism is a rare complication of chronic myeloid leukemia (CML), observed in 1–2% of males [5]. Its occurrence is always related to a high white blood cell (WBC) count that induces formation of microaggregates, causing sludging in veins with blood stasis and reduced venous efflux from the corpora cavernosa. The most common long-term sequela is a massive thrombosis of the corpora cavernosa with irreversible fibrosis and functional impotence. Many different approaches, such as cytotoxic drugs, cell depletion by leukapheresis, spinal irradiation, anticoagulants, fibrinolysins, multiple punctures of the corpora cavernosa, or surgical intervention of cavernospongiosum shunt, have been used to promptly resolve this complication in order to avoid the functional defect [1–4]. However, at present, there is no agreement on the best therapeutic management of this rare complication.

Differences in hematological and non-hematological toxicity during treatment with imatinib in patients with early and late chronic phase chronic myeloid leukemia

Imatinib is a relatively specific inhibitor of the BCR/ABL tyrosine kinase, effective in chronic myeloid leukemia (CML). The aim of our study was to analyse the frequency and type of hematological and non-hematological adverse events in our series of late and early chronic phase patients with CML treated with imatinib and correlate the grade of hematological toxicity with the response obtained. Hematological events were seen in 59 out of 150 (39%) late chronic phase (CP) patients: of these, 24% experienced toxicity Grade 3–4. Of the 100 early CP patients, 26 (26%) had hematological adverse event: 7% experienced toxicity Grade 3–4 (p = 0.0001). We found that only in early CP patients, the occurrence of hematological side effects of any grade within 6 months of therapy had a negative influence on cytogenetic response. We compared the incidence of non-hematological adverse events occurring in late and in early CP patients and found that in these latter, some side effects were more frequent, such as weight gain, periorbital edema, muscle cramps, skin rashes, diarrhea, weeping. On the contrary, we found that bone pain and hemorrhagic events were more common in late CP patients. Grade 3–4 adverse events were recorded at rates below 4% and decreased over time: in late CP patients hemorrhages and muscle cramps were the most common side effects of Grade 3–4, whereas in early CP patients, the most frequent events were nausea, weight gain and cutaneous rash. We have observed that hematological and non-hematological side effects during imatinib therapy are different among late and early CP patients and that severe hematological toxicity may influence cytogenetic response only in early CP patients.