Objective: Myeloid‐derived suppressor cells (MDSCs) facilitate tumor growth and development by suppressing T cell function; however, their role in acute myeloid leukemia (AML) remains unclear. Here, we investigated the immunosuppressive role and prognostic value of blasts with an MDSC‐like phenotype.Methods: CD11b⁺CD33⁺HLA‐DR⁻ MDSC‐like blasts from bone marrow mononuclear cells of patients with AML were analyzed. To investigate their T cell‐suppressing function, MDSC‐like blasts were isolated using flow cytometry and co‐cultured with CD8⁺ cytotoxic T cells and NB4 leukemic cells. Treatment outcomes were then compared between the MDSC‐like blasts low (≤9.76%) and high (>9.76%) groups to identify clinical significance.Results: MDSC‐like blasts showed higher expression of arginase‐1 and inducible nitric oxide synthase. Isolated MDSC‐like blasts significantly suppressed CD8⁺ T cell proliferation induced by phytohemagglutinin A. NB4 cell proliferation was significantly suppressed upon co‐culture with CD8⁺ cytotoxic T cells and partially restored upon co‐culture with MDSC‐like blasts. Patients with high MDSC‐like blasts at diagnosis showed substantially shorter overall survival and leukemia‐free survival relative to low MDSC‐like blasts patients, with subgroup analysis showing statistically significant differences in patients not receiving allogeneic hematopoietic stem cell transplantation.Conclusion: We demonstrated that MDSC‐like blasts drive AML‐specific immune‐escape mechanisms by suppressing T cell proliferation and restoring T cell‐suppressed NB4 cell proliferation, with clinically higher fractions of MDSC‐like blasts at diagnosis resulting in poor prognosis.

Eom YW, et al. Yonsei Med J. 2011 Nov;52(6):999-1007. http://dx.doi.org/10.3349/ymj.2011.52.6.999

Background/Aims: Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database.Methods: This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]).Results: The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS.Conclusions: Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.

Background: The response rate and survival improvement for rituximab, a CD20‐targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single‐arm, open‐label phase II study evaluated the survival efficacy of 2 years of rituximab‐maintenance therapy in patients with stage III–IV CD20‐positive MZL who had responded to first‐line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation. Methods: Prior to rituximab‐maintenance therapy, patients received 6–8 cycles of first‐line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m ² ), cyclophosphamide (750 mg/m ² ), and vincristine (1.4 mg/m ² ; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3‐week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3‐week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab‐maintenance therapy which was administered intravenously at a dose of 375 mg/m ² every 8 weeks for up to 12 cycles. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. Results: 47 patients were enrolled, of whom, 45 (96%) received rituximab‐maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first‐line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow‐up of 38.2 months, their observed 3‐year PFS rate was 81%. During the rituximab‐maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS ( P = 0.003) and demonstrated a 3‐year OS rate of 90%. Rituximab‐maintenance therapy was well tolerated, and the common treatment‐emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). Conclusion: Rituximab‐maintenance therapy following first‐line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov : NCT01213095

Hwang HW, et al. Korean J Hematol. 2012 Mar;47(1):80-82. http://dx.doi.org/10.5045/kjh.2012.47.1.80

We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4–190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >3 TKIs (3 TKIs, n = 33; 4 TKIs, n = 17; 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6; myeloid blastic phase, n = 4; lymphoid blastic phase, n = 9). One third (n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1–53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.