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The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9–8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8–7.3) on VKA and 8.9 (95% CI: 5.7–13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2–8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3–20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19–5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1–4.5) on VKA and 0.7 (95% CI: 0.08–2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

Summary In the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy × 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was “purged” with in vitro technique, this review seems to confirm the importance of “in vivo” purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to drow final conclusions.

Various lines of evidence suggest that substantial numbers of very primitive normal hematopoietic cells persist in the marrow of most patients with CML, despite the presence of an expanded Philadelphia-Chromosome (Ph) positive population, and that normal clones might, in certain circumstances, have a proliferative advantage over leukemic populations. We have recently demonstrated in 5/8 CML patients with blastic phase (BP) that the blood progenitor cells/(BPC) harvested during early recovery from marrow aplasia were Ph-negative on cytogenetic analysis, suggesting that leukapheresis may provide a useful source of 'normal' progenitors for subsequent reinfusions. We report here an update on 40 patients with Ph + CML and 9 patients with ALL in first or subsequent relapses with associated cytogenetic translocations including t(8;14) t(4;8) t(4;11) and t(9;22). All these patients received intensive conventional chemotherapy and during early recovery from marrow aplasia, when the WBC reached 0.5-2.0 × 109/L, BPC were collected by 4-8 leukapheresis and tested for the persistence of the marker translocations and, when possible, for the presence of the hybrid bcr/abl transcripts by polymerase chain reaction (PCR). In seven out of 10 patients with chronic phase CML, BPC were Ph-negative and in 5 PCR negative. In both accelerated phase patients, BPC were Ph-negative but PCR-positive and in eight out of 28 blastic CML patients, BPC were Ph-negative and in two cases also PCR-negative. Six out of 9 ALL patients, lost the cytogenetic translocations. After complete recovery, 16 patients were subsequently given high-dose therapy followed by reinfusion of 'normal' BPC. Two patients in CP-CML and 2 out of six patients with ALL maintain clinical and cytogenetic remission at 3 and 10 months and 16 months respectively. All the patients transplanted in BP-CML relapsed 5-18 months post-transplant. These data suggest that intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal BPC.

Imatinib mesylate (IM) is a powerful and selective p210 Bcr-Abl tyrosine kinase inhibitor that has been demonstrated to be effective for the treatment of CML. An Italian multicenter study was performed to investigate the safety, efficacy, tolerance and compliance of IM in newly diagnosed CML patients. From February 2000 through February 2007, we collected 339 CML patients in different phases of disease and previously treated with Interferon-alpha and/or other therapies. One hundred fifty-two untreated Ph+ CML patients received Imatinib at diagnosis at a dose of 400 mg orally per day; 88 were male and 64 female with a median age of 50 (range, 17–80) years. Complete hematological remission was achieved in 94% of patients. The estimated rate of complete cytogenetic remission (CCR) was 69% after 12 months; with a median follow up of 38 months the rate of CCR raised to 86,8%. Levels of Bcr-Abl transcripts had fallen by at least 3 log in 59% of cytogenetic remitters patients at 12 months; after a median follow up of 38 months, 26% of these patients achieved complete molecular remission (CMR). The most commonly reported adverse events after IM were edema (including peripheral and periorbital edema) (50%), muscle cramps (37,7%), diarrhea (40,7%), fatigue (38,8%); moreover in 8 (5,2%) patients grade 3–4 events were observed consisting of pancitopenia and/or elevated liver enzymes. Eight (5,2%) patients died: 2 patients for progressive disease after allografting, 2 patients of cardiac infarction, 1 patient of severe necrotic fascitis, 1 patient of metastatic colon cancer and 2 patients of blastic crisis. In summary, at 84 months 144/152 (94,7%) patients are alive and 125 (86,8%) of them are still receiving IM. Nineteen (13%) patients discontinued Imatinib: 7 patients for adverse events grade 3–4 and 12 patients for progressive disease. These data are comparable to those of IRIS study and confirm the safety and efficacy of IM in newly diagnosed patients.

Imatinib mesylate (IM) is a powerful and selective p210 Bcr-Abl tyrosine kinase inhibitor that has been demonstrated to be effective for the treatment of CML. An Italian multicenter study was performed to investigate the safety, efficacy, tolerance and compliance of IM in newly diagnosed CML patients. From February 2000 through February 2007, we collected 339 CML patients in different phases of disease and previously treated with Interferon-alpha and/or other therapies. One hundred fifty-two untreated Ph+CML patients received Imatinib at diagnosis at a dose of 400 mg orally per day; 88 were male and 64 female with a median age of 50 (range, 17–80) years. Complete hematological remission was achieved in 94% of patients. The estimated rate of complete cytogenetic remission (CCR) was 69% after 12 months; with a median follow up of 38 months the rate of CCR raised to 86,8%. Levels of Bcr-Abl transcripts had fallen by at least 3 log in 59% of cytogenetic remitters patients at 12 months; after a median follow up of 38 months, 26% of these patients achieved complete molecular remission (CMR). The most commonly reported adverse events after IM were edema (including peripheral and periorbital edema) (50%), muscle cramps (37,7%), diarrhea (40,7%), fatigue (38,8%); moreover in 8 (5,2%) patients grade 3–4 events were observed consisting of pancitopenia and/or elevated liver enzymes. Eight (5,2%) patients died: 2 patients for progressive disease after allografting, 2 patients of cardiac infarction, 1 patient of severe necrotic fascitis, 1 patient of metastatic colon cancer and 2 patients of blastic crisis. In summary, at 84 months 144/152 (94,7%) patients are alive and 125 (86,8%) of them are still receiving IM. Nineteen (13%) patients discontinued Imatinib: 7 patients for adverse events grade 3–4 and 12 patients for progressive disease. These data are comparable to those of IRIS study and confirm the safety and efficacy of IM in newly diagnosed patients.