Relapse after stem cell transplantation for Philadelphia chromosomeÀpositive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first-generation TKI imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph+ ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). We performed database searches (inception to January 2018) using PubMed, Cochrane Library, and Embase. After exclusions, 17 articles were included in this analysis. Imatinib was used post-transplant either prophylactically or preemptively in 12 studies, 7 prospective studies and 5 retrospective studies. Overall survival (OS) for most prospective studies at 1.5 to 3 and 5 years ranged between 62% to 92% and 74.5% to 86.7%. Disease-free survival at 1.5 to 5 years was 60.4% to 92%. Additionally, imatinib failed to show survival benefit in patients who were >CR1 at the time of allo-HSCT. The cumulative OS for most retrospective studies using imatinib at 1 to 2 and 3 to 5 years was 42% to 100% and 33% to 40% respectively. Event-free survival at 1 to 2 and 3 to 5 years was 33.3% to 67% and 20% to 31% respectively. Dasatinib was used as maintenance treatment in 3 retrospective studies (n = 34). The OS for patients with Ph+ ALL using dasatinib as maintenance regimen after allo-HSCT at 1.4 to 3 years was 87% to 100% and disease-free survival at 1.4 to 3 years was 89% to 100%. Ninety-three percent of patients with minimal residual disease (MRD) positive status after allo-HSCT became MRD negative. Three prospective studies used nilotinib. In 2 studies where investigators studied patients with advanced chronic myeloid leukemia and Ph+ ALL, the cumulative OS and event-free survival at 7.5 months to 2 years were 69% to 84% and 56% to 84%, respectively. In the third study (n = 5) in patients with Ph+ ALL, nilotinib use resulted in OS at 5 years of 60%. Our review showed that use of TKIs (all generations) after allo-HSCT for patients in CR1 improved OS when given as a prophylactic or preemptive regimen. Limited data suggest that second-generation TKIs (ie, dasatinib) have a better OS, especially in patients with MRD-positive status. Imatinib did not improve OS in patients who were >CR1 at the time of allo-HSCT; for this population, no data were available with newer generation TKIs. The evaluation of survival benefit with newer generation TKIs and their efficacy in patients in >CR1 needs further study in large randomized clinical trials.

Multiple Myeloma (MM) is primarily a disease of old age with a median age of sixty-nine years at diagnosis. The development of novel therapies for induction and use of autologous stem cell transplantation has resulted in improved clinical outcomes and better quality of life for MM patients. Elderly patients, comprising the majority of MM population, have a higher incidence of age-related comorbidities, frailty and organ dysfunction which complicates the coordination of treatment and limits the selection of therapies. Even in the era of multiple chemotherapeutic options, the clinical heterogeneity of the myeloma patients' demands personalized treatments which often require dose-adjustments or dose delays. The use of reduced-dose regimens and various comorbidity indices has improved clinical outcome and regimen tolerability in MM patients with renal, neurological and bone abnormalities. We focus on advancements in the treatment of multiple myeloma with the goal to guide clinicians towards patient-specific management.

We present an unusual case of hyponatremia in an ambulatory hypothyroid patient and review related published literature on PubMed including, original articles, reviews and case reports that describe or refute the association and mechanism for the development of hyponatremia in hypothyroidism.A 50-year-old female presented in ambulatory clinic with complaints of bilateral hand swelling, fatigue, dizziness, and unsteadiness while walking. Laboratory investigations revealed that she had hypothyroidism and hyponatremia. Thyroid hormone replacement therapy resulted in resolution of hypothyroidism symptoms as well as hyponatremia. A comprehensive search of related literature regarding the development of chronic hyponatremia in hypothyroidism revealed two schools of thought, which we have summarized in this report.Based on our observations, we conclude that due to overlap in symptoms of hyponatremia and neurological manifestations of hypothyroidism, it is imperative to screen hypothyroid patients for underlying hyponatremia and treat accordingly in order to prevent long-term complications of chronic hyponatremia. Hyponatremia secondary to hypothyroidism resolves with appropriate thyroid hormone replacement therapy, which shows convincing evidence of an association between the two entities.

Restoration of immune response by highly active antiretroviral therapy (HAART) effectively improved the overall prognosis of HIV infection. However, 25%-31.7% of patients experience paradoxical worsening of pre-existing infections or unmasking of subclinical infections after starting HAART therapy, which is termed as immune reconstitution inflammatory syndrome (IRIS). Acute granulomatous interstitial nephritis as a consequence of IRIS has never been reported with coinfection. Here, we describe an HIV/AIDS patient coinfected with disseminated infection, who presented with acute kidney injury 4.5 months after initiation of HAART. The diagnostic workup revealed IRIS was the cause of acute kidney injury. Short-term course of prednisone (1 mg/kg/day) along with antimycobacterial and HAART regimen achieved significant improvement.

When comparing group 4 (median OS >9 years) to the other groups (median OS <9 years), younger age at MM diagnosis, frontline SCT, treatment at a high-volume cancer center, no associated comorbidities, female sex, insured, and median household income were associated with long-term survival in a multivariate analysis. The Table 2 shows univariate and multivariate odds ratio for long-term MM survival. Conclusion: Among patients with MM diagnosed between 2004 and 2006, 1 in 8 patients were long-term survivors (OS > 3X the median). Although differences in the underlying disease biology could not be assessed, key differences in socio-demographic characteristics, patient volume at treatment facility and use of SCT were associated with longterm survival. While some features at MM diagnosis cannot be changed (age, sex, associated comorbidities), early use of SCT and treatment at a high-volume cancer center at the time of diagnosis might impact long-term OS.