5‐Azacitidine Monotherapy Followed by Related Haploidentical Hematopoietic Stem Cell Transplantation Achieves Durable Remission in a Pediatric Patient With Acute Undifferentiated Leukemia Refractory to High‐Dose Chemotherapy

Patients with acute leukemias of undifferentiated lineage (AUL) generally have guarded prognosis. Here, we describe the first reported pediatric patient with AUL refractory to high‐dose chemotherapy who achieved clinical remission with ALL maintenance therapy and 5‐azacitidine. His induction remission was followed by consolidation with reduced toxicity haploidentical hematopoietic stem cell transplant (HSCT). At 9 months post‐HSCT, the patient is alive and in remission. This combination therapy of remission induction with ALL maintenance therapy and 5‐azacitidine and consolidation with reduced toxicity haploidentical HSCT is novel and promising for patients who lack conventional donors and are not candidates for myeloablative therapy.     

Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus

Human immunodeficiency virus (HIV) elicits the production of virus-specific antibodies in infected individuals. We investigated the ability of serum from HIV-infected individuals to mediate antibody-dependent cellular cytotoxicity in an in vitro 51Cr release assay system. Fresh peripheral blood mononuclear cells from healthy donors seronegative for HIV were used as cellular effectors against HIV-infected and uninfected H9 target cells in the presence of serum from HIV-infected or uninfected donors. Serum from HIV-infected, but not uninfected, donors significantly augmented cytolysis of virus-infected targets (P less than .005). There was no augmented killing of uninfected H9 cells with sera from either group. Studies using serum from mice that had been immunized with synthetic peptides from the HIV envelope region suggested that this response is directed, at least in part, at several determinants of the transmembrane portion of the HIV envelope glycoprotein.     

Overcoming Psychosocial and Developmental Barriers to Blood and Marrow Transplantation (BMT) in an Adolescent/Young Adult (AYA) Transgender Patient with Chronic Myelogenous Leukemia

Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.     

The major 40-kDa glycoprotein in human prostatic fluid is identical to Zn-alpha 2-glycoprotein

A major 40-KDA protein secreted by human prostate was isolated from whole seminal plasma by sequential column chromatography on DEAE-Sepharose CL-6B, concanavalin A(Con A)-Sepharose, and Sephadex G-100. Although the purified preparation still contained minor contaminants, its amino acid composition was found to be identical to the one of a glycoprotein isolated previously from seminal plasma by Lin et al (1983). Antibodies against this protein were produced in rabbits and their use in immunoblotting experiments revealed the presence of the antigen in several tissues including the prostate, the liver, the heart, the kidney, the epididymis, and the testis. A radioimmunoassay confirmed these results and showed that blood serum concentrations of this protein were relatively high in men (81 +/- 3 micrograms/ml), women (68 +/- 3 micrograms/ml), and cord blood of newborns (32 +/- 1 micrograms/ml). The serum concentrations of this protein along with its physicochemical characteristics suggested that it could be identical to Zn-alpha 2-glycoprotein, a human serum protein previously isolated by Burgi and Schmid (1961). This hypothesis was confirmed by a double immunodiffusion analysis using a commercial anti-Zn-alpha 2-glycoprotein antiserum. Finally, in vitro translation of prostatic poly(A) + RNA in rabbit reticulocyte lysate in the presence of canine pancreatic microsomal membranes resulted in the formation of an immunoprecipitable 42-kDa band. These results show that Zn-alpha 2-glycoprotein can be synthesized in the prostate itself. The demonstration of high concentrations of this protein in prostatic tissue and prostatic secretion should facilitate the elucidation of its role in the prostate and in other tissues.     

Entry-into-human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients

AIMS: To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). METHODS: This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. RESULTS: All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. CONCLUSIONS: SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.     

Pressor drugs in the treatment of cardiac arrest

The importance of vital organ perfusion in patients suffering cardiac arrest makes arterial vasomotor tone, and the resultant perfusion pressure, critical in resuscitation from sudden death. Although there are multiple mechanisms that may affect arterial vascular tone, historically, the therapy most commonly used has been catecholamine-induced adrenergic receptor stimulation, with catecholamine epinephrine being the commonest drug used. Over the last decade, however, it has become widely known that the utility of epinephrine during cardiopulmonary resuscitation is undefined. This has led to research into alternative agents, in particular nonadrenergic vasoactive peptides. Other agents appear promising. This article addresses pressor drugs and adrenergic agonists, including a review of their history, basic science, mechanism of action, and efficacy. Epinephrine is reviewed.