Achieving a Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long Term Outcome

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P\u2009=\u2009.007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P\u2009=\u2009.17) and overall survival was 58% versus 49% (P\u2009=\u2009.55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation

Prognostic implications of anemia in older adults

Anemia is highly prevalent in geriatric practice. In this perspective article, Dr. Patel and Guralnik conclude that this condition is associated with adverse health and functional outcomes in older persons. See related article on page 22

Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL)

Clinical risk classification is inaccurate in predicting relapse in adult patients with acute lymphoblastic leukemia, sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation (SCT). We studied minimal residual disease (MRD) as a predictive factor for recurrence and as a decisional tool for postconsolidation maintenance (in MRD(neg)) or SCT (in MRD(pos)). MRD was tested at weeks 10, 16, and 22 using real-time quantitative polymerase chain reaction with 1 or more sensitive probes. Only patients with t(9; 22) or t(4; 11) were immediately eligible for allogeneic SCT. Of 280 registered patients (236 in remission), 34 underwent an early SCT, 60 suffered from relapse or severe toxicity, and 142 were evaluable for MRD at the end of consolidation. Of these, 58 were MRD(neg), 54 MRD(pos), and 30 were not assessable. Five-year overall survival/disease-free survival rates were 0.75/0.72 in the MRD(neg) group compared with 0.33/0.14 in MRD(pos) (P = .001), regardless of the clinical risk class. MRD was the most significant risk factor for relapse (hazard ratio, 5.22). MRD results at weeks 16 to 22 correlated strongly with the earlier time point (P = .001) using a level of 10(-4) or higher to define persistent disease. MRD analysis during early postremission therapy improves risk definitions and bolsters risk-oriented strategies. ClinicalTrials.gov identifier: NCT00358072

Mortality rate and risk factors for gastrointestinal bleeding in elderly patients

Background: Gastrointestinal bleeding (GIB) is burdened by high mortality rate that increases with aging. Elderly patients may be exposed to multiple risk factors for GIB. We aimed at defining the impact of GIB in elderly patients. Methods: Since 2008, samples of elderly patients (age 65 65 years) with multimorbidity admitted to 101 internal medicine wards across Italy have been prospectively enrolled and followed-up (REPOSI registry). Diagnoses of GIB, length of stay (LOS), mortality rate, and possible risk factors, including drugs, index of comorbidity (Cumulative Illness Rating Scale [CIRS]), polypharmacy, and chronic diseases were assessed. Adjusted multivariate logistic regression models were computed. Results: 3872 patients were included (mean age 79 \ub1 7.5 years, F:M ratio 1.1:1). GIB was reported in 120 patients (mean age 79.6 \ub1 7.3 years, F:M 0.9:1), with a crude prevalence of 3.1%. Upper GIB occurred in 72 patients (mean age 79.3 \ub1 7.6 years, F:M 0.8:1), lower GIB in 51 patients (mean age 79.4 \ub1 7.1 years, F:M 0.9:1), and both upper/lower GIB in 3 patients. Hemorrhagic gastritis/duodenitis and colonic diverticular disease were the most common causes. The LOS of patients with GIB was 11.7 \ub1 8.1 days, with a 3.3% in-hospital and a 9.4% 3-month mortality rates. Liver cirrhosis (OR 5.64; CI 2.51\u201312.65), non-ASA antiplatelet agents (OR 2.70; CI 1.23\u20135.90), and CIRS index of comorbidity >3 (OR 2.41; CI 1.16\u20134.98) were associated with GIB (p < 0.05). Conclusions: A high index of comorbidity is associated with high odds of GIB in elderly patients. The use of non-ASA antiplatelet agents should be discussed in patients with multimorbidity

Polypharmacy in older people: lessons from 10\ua0years of experience with the REPOSI\ua0register

As a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration and\ua0inevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug\u2013drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society of Internal Medicine chose to start in 2008 a prospective register called REPOSI (REgistro POliterapie SIMI, Societ\ue0 Italiana di Medicina Interna) in internal medicine and geriatric hospital wards. The country wide register is an ongoing observatory on multimorbidity and polypharmacy in the oldest old, with the goal to improve prescription appropriateness and, thus to avoid potentially inappropriate medications. The main findings of the register, that has accrued so far, 7005 older patients throughout a 10\ua0year period, are summarized herewith, with special emphasis on the main patterns of poor prescription appropriateness and related risks of adverse events