The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison.

The treatment of older patients with acute myeloid leukaemia, who are not considered suitable for conventional intensive therapy, is unsatisfactory. Low-dose Ara-C(LDAC) has been established as superior to best supportive care, but only benefits the few patients who enter complete remission. Alternative or additional treatments are required to improve the situation. This randomised trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO), at a dose of 5 mg on day 1 of each course of LDAC, with the intention of improving the remission rate and consequently survival. Between June 2004 and June 2010, 495 patients entered the randomisation. The addition of GO significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32-0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason for the induction benefit failing to improve OS was two-fold: survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm. Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival. Maintaining remission in older patients remains elusive.

Autologous peripheral blood stem cell transplantation in first remission adult acute myeloid leukaemia--an intention to treat analysis and comparison of outcome using a predictive model based on the MRC AML10 cohort.

The role of autologous peripheral blood stem cell transplantation (APBSCT) in acute myeloid leukaemia (AML) remains controversial. The current study evaluated the application of APBSCT in a large consecutive series of patients with untreated AML, and compared outcome with a predictive model based on MRC AML10 data. Of 148 evaluable patients, 118 patients entered complete remission (CR) after induction therapy comprising three cycles of daunorubicin, cytosine arabinoside and oral 6-thioguanine. Of these patients, 68 (57%) proceeded to consolidation therapy with two courses of intermediate dose cytosine arabinoside, and stem cell mobilisation, and 40 of these patients (34%) underwent the APBSCT procedure after high dose busulphan conditioning. Harvest quality was the main factor precluding APBSCT. Five-year event-free survival (EFS) in patients who achieved CR was 38% and in APBSCT patients was 57%. There were no transplant-related deaths. No significant differences were demonstrated between observed and expected outcomes at 1 and 2 years, based on the predictive model derived from the MRC AML10 study. These data therefore indicate that only a third of eligible adult patients will undergo APBSCT. However, the results demonstrate favourable survival in such patients, with no transplant-related mortality.

Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study.

A multicenter phase II study was initiated to investigate the efficacy, toxicity and tolerability of an oral regimen of 9-cis retinoic acid (9CRA) as a differentiation-inducing agent stimulating both retinoic acid receptor (RAR) and retinoic X receptor (RXR). Thirty patients with myelodysplastic syndromes (MDS) were enrolled into the study. The MDS subtypes were distributed as follows: 14 refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), and 12 refractory anaemia with excess blasts (RAEB). The age ranged from 40 to 81 years (median 70). None of these had previously received treatment for MDS other than supportive therapy. 9CRA (Alitretinoin capsules, kindly provided by Allergan-Ligand Retinoid Therapeutics) was given daily at 60 mg/m2 p.o. for 1 week, followed by an intra-patient escalation to 100 mg/m2 during the second week, up to a maximum of 140 mg/m2. The planned treatment duration was 48 weeks. Twenty-five were available for assessment. One patient (4%) with RA achieved complete hematological remission. Four (16%), two with RA, two with RAEB, had minor responses resulting in decreased transfusion requirements or increased neutrophils. Thus, the overall response rate was 20% in evaluable patients with MDS and 17% in the study group on an intention-to-treat basis. The most frequent side-effects included headache (77%), dry skin (57%), arthralgias (30%), and rash (23%). In conclusion, although modest responses were noted in this study, the treatment tolerability was suboptimal. It is conceivable that a lower dosage schedule may be efficacious and better tolerated so enabling prolonged exposure which may be required to induce a differentiation effect.