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Objective Overexpression of ABCG2 and CD200 has been independently associated with poor outcome in acute myeloid leukemia ( AML). However, no data are available on the role of these two factors in patients with core-binding factor ( CBF)-positive or FLT3-negative/ NPM1-mutated cytogenetically normal ( CN) AML. Methods We analyzed 65 adult AML patients with CBF+ (n=16) or FLT3−/ NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia-free survival ( LFS) and overall survival ( OS). Results ABCG2 was expressed in 36 (55%) cases, and CD200 was positive in 33 (51%) cases, six at high levels. Both ABCG2 and CD200 positivity have a negative impact on relapse risk: 3-year LFS was 51% vs 82% in ABCG2+ cases ( RR 3.3), 49% vs 82% in CD200+ patients ( RR=4.4), and 25% in CD200− high cases ( RR=17.1). ABCG2 and CD200 affected also OS with 3-year OS of 39% in ABCG2+ (compared to 71% in ABCG2−; RR=2.6) and CD200+ (compared to 68% in CD200−; RR=2.5) patients. Conclusions Our data confirm a negative impact of ABCG2 and CD200 overexpression also in AML patients considered at favorable risk according to ELN cytogenetic/molecular classification. [ABSTRACT FROM AUTHOR]

Candoni A, Toffoletti E, Gallina R, Simeone E, Chiozzotto M, Volpetti S, Fanin R. Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin Transplant 2011: 25: 308-316. © 2010 John Wiley & Sons A/S. WT1 is well-known to be a panleukemic marker that is expressed in 90% of acute myeloid leukemias (AML). Quantification of WT gene expression in bone marrow (BM) samples may be useful as a marker of minimal residual disease (MRD) during and after treatment for early prediction of relapse. We evaluated the validity of this AML-MRD marker after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). The quantitative assessment of WT1 expression by real-time quantitative PCR (RQ-PCR) was measured in 25 patients (pts) with AML at diagnosis, at the time of RIC-SCT and after transplant at precise time points. All pts showed high WT1 levels at diagnosis with a mean of 4895 (SD 4462) and a median of 3679 (range 454-16 853) copies WT1/10 ABL. At transplant, 18/25 pts (72%) were in complete cytologic remission (CcR) and 7/25 (28%) had refractory AML. At the pre-SCT evaluation, BM samples from pts transplanted in CcR showed significantly lower WT1 expression levels compared to the samples from pts with refractory AML (p = 0.002). Median follow-up after RIC-SCT was 18 months (range 2-54). On 18 pts transplanted in CcR, those (17/18) who maintained CcR after RIC-SCT displayed a WT1 copy number persistently low during all the follow-up period. In patients who received RIC-SCT with active disease obtaining a sustained CcR after transplant (3/25), WT1 levels decreased to normal range in the first two months after RIC-SCT and remained low through the entire study period. All pts who relapsed after RIC-SCT (4/25) had a high WT1 copy number before the cytologic relapse. In 50% of these cases, an increase in WT1 expression was documented before molecular chimerism decreasing. With this experience, taking into account the limited number of pts, we confirmed a concordance between WT1 expression levels (measured by RQ-PCR at precise and sequential time points) and status of AML before and after RIC-SCT and we found a concordance between WT1 expression levels and hematopoietic chimerism status. Our data suggest that, in the RIC-SCT setting, the sequential and quantitative analysis of WT1 may be useful as a leukemia marker for monitoring MRD and as a predictor of overt AML cytologic relapse. [ABSTRACT FROM AUTHOR]

Introduction Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease. Patients and results we report the clinical characteristics and outcome of 48 histologically confirmed MS, diagnosed and treated in 9 Italian Hematological Centers in the last 10 years. The patient’s median age was 46 years. There were 9/48 de novo extramedullary MS, 24/48 de novo AML-related MS and 15/48 were secondary AML-related MS. The most common extramedullary anatomic sites of disease were: skin, lymph nodes and soft tissues. Forty-three patients (90%) underwent a program of intensive chemotherapy including FLAI, HDAC-IDA, HyperCVAD and MEC schemes, with a DDI of 5% and a CR Rate of 45%. Twenty-two (46%) patients underwent Allogeneic SCT, 13 from a MUD, 8 from an HLA-identical sibling donor and 1 from an haploidentical donor. The median OS of the whole population (48 pts) was 16.7 months. The OS probability at 1, 2 and 5 years was 64%, 39% and 33%, respectively. The OS was better in patients that underwent an intensive therapeutic program (median OS: 18 months vs 5 months). Among the intensively treated patients, in univariate analysis, the OS was better in young patients (P = 0,008), in patients that underwent Allo-SCT (P = 0,009) and in patients that achieved a CR during treatment (P = 0,001), and was worse in pts with secondary AML-related MS (P = 0,007). Age, response to intensive chemotherapy and Allo-SCT were the only three variables that significantly influenced DFS (P = 0,02, P = 0,01 and P = 0,04, respectively). In multivariable analysis, Allo-SCT and response to intensive chemotherapy remained significant in predicting a better OS (P = 0,04 and P = 0,001, respectively), and response to intensive chemotherapy was the only significant variable in predicting DFS (P = 0,01). After Allo-SCT we observe a survival advantage in patients who achieved a pre-transplant CR (P = 0,008) and in those who developed a chronic GvHD (P = 0,05). Conclusions Patients with MS, both with de novo and secondary forms, still have a very unfavorable outcome and require an intensive therapeutic program, that includes Allo-SCT whenever possible. The outcome after Allo-SCT is positively influenced by the development of chronic GvHD suggesting a Graft versus MS effect. [ABSTRACT FROM AUTHOR]

Abstract: Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation (SCT) is dismal. Immunotherapy with donor lymphocyte infusion (DLI) and imatinib are rarely and/or transiently effective. Here we describe the case of a patient with imatinib-resistant post-transplant relapse of ALL, who received a combination of standard dose nilotinib and monthly DLI infusion. Therapy was well tolerated and the patient achieved and maintained a complete molecular remission. Our case provides a rationale for the combined use of a second line tyrosine kinase inhibitor and DLI in the treatment of relapsed Ph+ ALL. [Copyright &y& Elsevier]