Acute myeloid leukemia: current progress and future directions

Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.Subject terms: Prognosis, Health services     

Use of quantitative competitive PCR to measure Epstein-Barr virus genome load in the peripheral blood of pediatric transplant patients with lymphoproliferative disorders.

A quantitative competitive PCR (QC-PCR) assay for Epstein-Barr virus (EBV) has been developed to provide accurate measurement of EBV genome load in pediatric transplant recipients at risk for developing posttransplant lymphoproliferative disorder (PTLD). The assay quantifies between 8 and 5,000 copies of the EBV genome in 10(5) lymphocytes after a 30-cycle amplification reaction. For 14 pediatric patients diagnosed with PTLD, the median EBV genome load was 4,000, and 13 of the 14 patients had values of >500 copies per 10(5) lymphocytes. Only 3 of 12 control transplant recipients not diagnosed with PTLD had detectable viral genome loads (median value, 40). This median was calculated by using the highest value obtained by PCR testing on each of these patients posttransplantation. PCR values of >500 copies per 10(5) lymphocytes appear to correlate with a diagnosis of PTLD. By a modified protocol, the EBV genome copy number in latently infected adults was estimated to be <0.1 copy per 10(5) lymphocytes.     

Meta-Analysis and Systematic Review of Micro- and Macro-Nutrient Intakes and Trajectories of Macro-Nutrient Supply in the Eastern Mediterranean Region

The Eastern Mediterranean Region (EMR) is experiencing a nutrition transition, characterized by the emergence of overnutrition and micro-nutrient deficiencies. No previous study has comparatively examined nutrient intake in adults across countries in the EMR. This review examined the adequacy of nutrients in adults living in the EMR. Moreover, it analyzed the food balance sheets (FBS) for 1961–2018 to identify the trajectory of energy supply from macro-nutrients in the EMR. A systematic search was conducted from January 2012 to September 2020. Only observational studies were retained with a random sampling design. An assessment of the methodological quality was conducted. Levels of nutrient daily intake and their adequacy compared to the daily reference intake of the Institute of Medicine were reported across the region. No studies were identified for half of the region’s countries. Although nutrient energy intake was satisfactory overall, fat and carbohydrate intake were high. Intake of vitamin D, calcium, potassium, zinc, and magnesium were below that recommended. The analysis of the FBS data allowed for the identification of four linear patterns of trajectories, with countries in the EMR best fitting the ‘high-energy-supply from carbohydrate’ group. This systematic review warrants multi-sectorial commitment to optimize nutrient intake.     

Primary percutaneous approach to upper urinary tract transitional cell carcinoma

The optimal approach to upper tract TCC remains to be redefined. A routine nephroureterectomy for every filling defect in the upper urinary system, even in the case of a normal contralateral kidney, constitutes an unnecessary mutilation in more than two thirds of the cases. Nephroureterectomy does not reduce the need for a long-term cystoscopic follow-up because of the high rate of bladder tumor recurrence that may happen years later after nephroureterectomy. Relying solely on radiography and cytology, lacking sensitivity and specificity, to recommend a nephroureterectomy is against the principles of oncologic surgery, especially now that preoperative histologic proof is easy to obtain endoscopically without compromising cancer control. Ureteroscopy, rigid and flexible, provides a complete assessment of the upper urinary system. Biopsy specimens taken with ureteroscopy may be sufficient for grading but less adequate for staging of the tumor. The authors reserve ureteroscopy for ureteral tumors and small (< 1.5 cm) single tumors of the renal pelvis. They approach large or multiple tumors of the renal pelvis percutaneously, in which a full histologic assessment is possible along with a complete resection of the tumor. The decision on the therapeutic approach is made only after the final pathologic report is reviewed. Grade I and grade II superficial disease (Ta, T1) can be treated endoscopically with minimal morbidity and with an efficiency comparable with the standard more invasive nephroureterectomy (Table 5). The indications for endourologic treatment in these cases can be extended safely beyond a solitary kidney or a high surgical risk to include any healthy individual with a normal contralateral kidney who is willing to commit to a rigorous lifelong follow-up. Patients with grade II T1 lesions require a more vigilant follow-up. For grade III Ta disease, more caution should be exercised in selecting these patients for elective endourologic management. When criteria of good prognosis are found, such as absence of carcinoma in situ, presence of diploidy, low p53 expression and a single-tumor, endoscopic management can be offered [table: see text] with a closer follow-up and resorting always to immediate nephroureterectomy at the first evidence of upstaging. Because of the high incidence of recurrence and progression, elective endourologic management for grade III T1 tumors is not recommended. Endoscopic conservative surgery still can be offered in the cases of a solitary kidney or chronic renal insufficiency or for poor surgical candidates. Patients with localized stages (T2, T3) TCC should be offered immediate nephroureterectomy. The authors do not expect adequate endoscopic extirpation with muscle invasive tumors. Although the tissue removed may include deep layers, deep resection is precluded by the thin renal pelvic wall and the associated risk for perforation. Patients with more extensive disease (T3, T4) have a bad prognosis regardless of the form of therapy. Achieving local control percutaneously while preserving as many nephrons as possible for the future chemotherapy can be a reasonable option.     

Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia.

PURPOSE: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent with significant antileukemia activity. A phase I study of cloretazine combined with cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease. DESIGN: Ara-C was given i.v. at a fixed dose of 1.5 gm/m(2)/d by continuous infusion for 4 days (patients ages <65 years at time of diagnosis) or 3 days (patients ages > or =65 years). Cloretazine was given i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m(2), with escalation in 100 mg/m(2) increments in cohorts of three to six patients until a maximum tolerated dose was established. The DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT) was measured at baseline. RESULTS: Forty patients, including 32 with acute myeloid leukemia, received 47 courses of treatment. Complete responses were seen at cloretazine dose levels of > or =400 mg/m(2) in 10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was significantly lower in patients that responded to treatment than in patients who did not (P < or = 0.027). Dose-limiting toxicities (gastrointestinal and myelosuppression) were seen with 500 and 600 mg/m(2) of cloretazine combined with the 4-day ara-C schedule but not seen with the 3-day schedule. CONCLUSION: The recommended cloretazine dose schedule for future studies is 600 mg/m(2) combined with 1.5 gm/m(2)/d continuous infusion of ara-C for 3 days. The cloretazine and ara-C regimen has significant antileukemic activity. AGT activity may be a predictor of response to cloretazine.     

Multivisceral organ failure related to leptospirosis in pregnant patient

Leptospirosis is the most widespread zoonosis in the world. It is caused by pathogenic leptospira infection. This infection is also an uncommon cause of hepatorenal failure. Indeed, hemolysis, elevated liver enzyme levels and low platelet count syndrome, and acute fatty liver of pregnancy are specific to the pregnant state. Leptospirosis is rarely described in pregnancy; it might mimic puerperal sepsis or hepatorenal failure associated with pregnancy induced hypertension. We report a case of leptospirosis presenting as multiple organ failure during third trimester of pregnancy with a good outcome.     

Erratum to: Musculoskeletal manifestations of primary hyperparathyroidism

Clinical Rheumatology -