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For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Purpose The main objective of this study is to gain a deeper understanding of how patients suffering from chronic myeloid leukemia (CML) cope with their illness. The study aims to reconstruct the subjective meaning-making process related to CML in order to gain insights into the impact the disease has on patients' emotions and everyday lives, as well as to explore the psychological impact of their being presented with the chance to suspend their therapy and recover from the disease. Methods Data were gathered from a qualitative study conducted in Italy on 158 Italian CML patients. Basing the study on the narrative inquiry approach, the patients were required to describe their patient journey in a qualitative narrative diary. These contained prompts to elicit the free expression of their needs, expectations, and priorities. A lexicographic analysis was carried out with T-LAB software and in particular a thematic analysis of elementary contexts (TAECs) and a word association analysis (WAA). Results The TAEC detected four thematic clusters related to two factors (temporal frame and contextual setting) that explained the variance among the narratives. The WAA evidenced a wide variety of emotions, both positive and negative, as patients reacted to the possibility of interrupting their therapy. Conclusions A better understanding of patients' experiences can offer insights into promoting the development of more sustainable healthcare services and into therapeutic innovation aimed at improving patients' quality of life and at engaging them more in their treatment. The findings of this study can also help make medical professionals more aware of the patient's burden and help them identify potential interactions and emotional levers to improve clinical relationships.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35–59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

Only few acute myeloid leukaemia (AML) relapsed patients achieve a long term survival after allogeneic haematopoetic stem cell transplantation (alloSCT). Adequate prognostic criteria are required for selecting patients (pts) who can benefit from this procedure. Aim of this study was to assess prognostic factors affecting OS in a cohort of 50 AML pts who received alloHSCT as salvage treatment after a risk-oriented frontline chemotherapy (NILG AML01-00). Fifty out of 140 pts in first relapse received allograft as salvage therapy. Median age was 50 yr (14 pts were >55). At diagnosis 31(62%) pts had high risk AML, defined by clinical and cytogenetic characteristics according to the NILG protocol. Median time from 1st CR to relapse (TTR) was 10 months (mo) and from relapse to allo was 3 mo. At alloSCT 34 pts (85%) were in 2nd CR, and 16 were transplanted with disease. The donor was matched related for 19 pts, matched unrelated for 22 and haploidentical for 9. Stem cell source was PB in 31, BM in 12 and CB in 7 pts. The conditioning regimen was myeloablative (MA) in 38 (74%) and reduced intensity (RIC) in 12. The impact of risk factors on OS was analyzed by univariate and multivariate analyses. The clinical outcome of the 50 transplanted pts was compared with 90 consecutive pts receiving other intensive salvage treatment. After alloSCT 44/50 (88%) achieved a 2nd CR. Relapse occurred in 22 pts at a median time of 8 mo from alloSCT, and all died. Among the 16 pts transplanted with disease 3 are in CCR. Acute (grade>II) or chronic GVHD occurred in 23 pts (46%). The 100dy- and 1-yr TRM was 6% and 20%. Among transplant related deaths, 75% were attributable to MA regimens. After a median follow up of 10 mo (range 3-68), median OS was 13 mo. The projected 1 yr- and 3-ys OS was 60 and 33%. Thirteen (28%) were in CCR at the end of follow-up. The 90 non transplanted pts showed a median OS of 3 mo, with a 1-yr OS of 16% (p=0.000). Univariate analysis performed on the 50 transplanted pts showed that high risk AML, TTR<6mo, ECOG-PS>0 and disease status at transplant were predictive of a poor outcome (p<0.05). By Cox multivariate analysis TTR<6mo and PS>0 were independent adverse prognostic factors for OS (p=0.04 and 0.01). Our data confirm that allograft can offer a better clinical outcome than other intensive regimen. Allograft should be proposed preferentially to pts with a TTR?6 mo and a very good PS.RIC seems to be as effective and less toxic than MA conditioning regimen, but larger prospective studies are required for confirming the role of RIC in AML salvage strategies.

Acute lymphoblastic leukemia (ALL) in adults is currently associated with an overall survival rate of around 40% at 5 years. This is an unsatisfactory result that makes it imperative to dissect further the biology of the disease in order to identify highly specific therapeutic targets to implement selectively the cure rate. The recognition of discrete ALL subsets followed by the application of risk-oriented therapies has been a major achievement over the past 30 years.

Purpose of ReviewLymphoblastic lymphoma (LBL) is a rare, highly aggressive non-Hodgkin lymphoma variant virtually indistinguishable from acute lymphoblastic leukemia (ALL). We review the advancements in diagnostics, staging, treatment, and response assessment.Recent FindingsT-LBL displays a mediastinal mass with pleuro-pericardic effusions as key distinctive features and is far more frequent than B-LBL. LBL is exquisitely sensitive to ALL-type chemotherapy, achieving cure rates in the order of 70% in adults and even more in children. Positron-emission tomography, genetic risk classifications, and minimal disseminated/residual disease assays are increasingly used to detect occult sites of involvement and predict treatment outcome. Stem cell transplantation is effective and should be considered for very high-risk subsets and/or at salvage.SummaryAlthough curable in the majority of patients, about 25–30% of adults with LBL patients experience resistance or relapse following first-line therapy. It is essential to identify these cases early on and to explore new modalities of precision medicine with targeted agents.