Anna Lambie

Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR.

Allo-SCT is potentially curative for patients with AML. Patients transplanted in CR2 tend to experience inferior survival compared with those in CR1. We retrospectively investigated the impact of pretransplant variables on the outcome of patients transplanted with AML in CR2. Ninety-four patients with AML in CR2 received a transplant between 1999 and 2011 with myeloablative (MA, n=65) or reduced-intensity conditioning regimens (RIC, n=29). Variables investigated included cytogenetic risk at diagnosis (SWOG), hematopoietic cell transplantation-specific comorbidity index (HCT-CI), CMV status, duration of CR1 and age. Median age of all patients was 47 years (range 18–70). Multivariable analysis for OS identified three prognostically significant categories: a favorable risk group included patients with duration of CR1 ⩾6 months, age <55 years and HCT-CI score 0–3, an intermediate risk group with duration of CR1 ⩾6 months, age <55 years and HCT-CI score 4–5 and a high-risk group with duration of CR1 <6 months or age ⩾55 years (P=0.0001) with 5-year survivals of 53%, 31% and 6%, respectively. Acute and chronic GVHD did not influence this risk stratification. The stated risk factors discriminate patients with different OS and may assist in decision making for allo-SCT.

Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2

For AML, older age, advanced disease and increased hematopoietic cell transplant comorbidity index (HCT-CI) are associated with worse prognosis following allogeneic hematopoietic cell transplantation (HCT). This single-center retrospective study investigated the influence of pre-transplant characteristics on outcomes of 387 patients undergoing allogeneic HCT for AML in CR1 and CR2. The multivariable analysis model for overall survival (OS) included age (hazard ratio (HR)=2.24 for ages 31–64 years and HR=3.23 for age ⩾65 years compared with age ⩽30 years, P=0.003), remission status (HR=1.49 for CR2 compared with CR1, P=0.005) and HCT-CI score (HR=1.47 for ⩾3 compared with <3, P=0.005). Transplant year was significantly associated with OS (P=0.001) but this did not influence the model. A weighted score was developed with age ⩽30, CR1 and HCT-CI score <3 receiving 0 points each, and CR2 and HCT-CI score ⩾3 receiving 1 point each. Ages 31–64 received 2 points, age ⩾65 received 3 points. Scores were grouped as follows: scores 0–1 (low risk, n=36), score 2 (intermediate–low risk, n=147), score 3 (intermediate–high risk, n=141) and scores 4–5 (high risk, n=63) with 3-year OS of 71%, 55%, 42% and 29% for scores 0–1, 2, 3 and 4–5, respectively (P<0.0001). The score predicted nonrelapse mortality (P=0.03) but not cumulative incidence of relapse (P=0.18). This model should be validated for the pre-HCT assessment of AML patients in CR1 and CR2.

Modified EBMT Pretransplant Risk Score Can Identify Favorable-risk Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for AML, Not Identified by the HCT-CI Score

INTRODUCTION Risk scores have been developed for allogeneic hematopoietic cell transplantation (HCT) outcomes, such as the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) and the modified European Group for Blood and Marrow Transplantation risk score (mEBMT) for acute leukemia. We investigated the influence of these scores for 350 patients who underwent transplantation for acute myeloid leukemia (AML). PATIENTS AND METHODS The HCT-CI scores were grouped as 0 to 2 and ≥ 3 (231 and 119 patients, respectively) and the mEBMT scores as 0 to 2 and ≥ 3 (166 and 184 patients, respectively). RESULTS Univariate analysis showed a significant association between the HCT-CI score and overall survival (OS) (P = .01), as did the mEBMT score (P = .002). The 5-year OS rate was 50% and 34% for a mEBMT score of 0 to 2 and ≥ 3, respectively. A subgroup of patients with a mEBMT score of 0 to 1 (n = 32) demonstrated a favorable OS of 75% at 5 years. This subgroup was younger (median age, 31 years), in first remission at transplantation, and had related donors. For the HCT-CI, the 5-year OS was 46% and 34% for a score of 0 to 2 and ≥ 3, respectively. Patients with an HCT-CI score of 0 (n = 94) had a 5-year OS of 44%. Multivariable analysis confirmed both the HCT-CI score and the mEBMT score, as previously grouped, as independent prognostic variables for both OS (P = .02 and P = .001, respectively) and nonrelapse mortality (NRM) (P = .01 and P = .003, respectively). CONCLUSION The results of the present study have demonstrated that the HCT-CI and mEBMT are both prognostic for OS and NRM in our cohort. However, the mEBMT score can identify a favorable-risk subgroup of patients not identifiable using the HCT-CI.

A comparison of long-term outcomes of donor lymphocyte infusions and tyrosine kinase inhibitors in patients with relapsed CML after allogeneic hematopoietic cell transplantation

BACKGROUND Donor lymphocyte infusion (DLI) and tyrosine kinase inhibitors (TKIs) are the 2 standard treatment options in chronic myeloid leukemia (CML) that relapses after hematopoietic cell transplantation (HCT), but reports comparing long-term outcomes of these modalities are rare. PATIENTS AND METHODS A total of 46 patients were treated with either DLI (n = 28) or TKIs (n = 18) during a first relapse of CML after HCT between 1993 and 2012. The stage of relapse was the chronic phase in 37 patients and the advanced phase in 9 patients. All patients had myeloablative conditioning without T-cell depletion during HCT. The median interval between HCT and treatment for relapse was 34 (range, 2-197) months. RESULTS At a median follow-up of 146 and 70 months, respectively, 32% of the DLI group and 33% of the TKI group had died. Six (21%) patients initially treated with DLI received TKIs during a second relapse. In multivariable analyses, DLI was associated with inferior overall survival (OS) (hazard ratio [HR], 37.4; 95% confidence interval [CI], 2.2-625.4; P = .01), shorter failure-free survival (FFS) (HR, 21.15; 95% CI, 1.8-251; P = .02), higher cumulative incidence of failure (CIF) (HR, 19.5; 95% CI, 1.6-236.5; P = .02), and increased incidence of treatment-induced graft vs. host disease (GVHD) (68% vs. 6%; P = .001). CONCLUSION TKIs appear better than DLI in chronic-phase relapses after myeloablative non-T-cell-depleted HCT. Outcomes were poor in advanced-phase relapses irrespective of treatment modality.

Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission

Secondary AML (sAML) has a poor prognosis with conventional chemotherapy alone. Allogeneic hematopoietic cell transplantation (HCT) is beneficial for high-risk AML. Data comparing outcomes of transplants for patients with de novo and sAML are limited. We compared outcomes of patients transplanted for de novo and sAML in first complete remission and investigated the effect of age, HCT comorbidity index (HCT-CI) and karyotype in both groups. A total of 264 patients with de novo (n=180) and sAML (n=84) underwent allogeneic HCT between 1999 and 2013. Median age at transplant was 51 years (range 18–71), median follow-up of survivors was 77 months. Evaluation of all patients demonstrated no significant difference between de novo and sAML for overall survival (P=0.18), leukemia-free survival (P=0.17), cumulative incidence of relapse (P=0.51) and non-relapse mortality (P=0.42). Multivariable and propensity score analyses confirmed the comparable outcomes between de novo and sAML post transplant. Although sAML demonstrates outcomes inferior to de novo AML treated with chemotherapy alone, outcomes following allogeneic HCT are comparable between the two groups.

Relationship between neurocognitive functioning and medication management ability over the first 6 months following allogeneic stem cell transplantation

Although neurocognitive impairment has been established as a major issue among cancer survivors, the real-world consequences of this impairment are unclear. This study investigated the relationship between neurocognitive functioning and medication management ability over time among 58 patients treated with allogeneic hematopoietic stem cell transplantation (HCT). Participants completed a neuropsychological test battery and a simulated medication management task at three time points: pre-transplant (T0), Day 100 (T1) and 6 months post transplant (T2). Neurocognitively impaired participants performed worse on the medication management task than neurocognitively normal participants at each time point, and were more likely to score in the impaired range of medication management ability post transplant (72% vs 20%, P<0.001 at T1; 67% vs 23%, P=0.013 at T2). In multivariate analyses, worse performance in executive functioning/working memory consistently predicted impaired medication management ability, even when controlling for sociodemographic and clinical confounders (odds ratio=0.89, 95% confidence interval (0.80, 0.98), P=0.023). Lower physical symptom distress also predicted impaired medication management ability, but this effect decreased over time. Self-reported cognitive problems were not correlated with medication management ability at any time point. Findings suggest that poor neurocognitive functioning, particularly in the domain of executive functioning/working memory, is associated with worse medication management ability within the first 6 months after allogeneic HCT.