Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation.

Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in randomized trials.

Spontaneous Pregnancy in the Setting of Primary Ovarian Insufficiency and Breastfeeding: Does Immunosuppression Play a Role?

BACKGROUND Primary ovarian insufficiency is defined as primary hypogonadism in a woman under the age of 40 years. It commonly presents clinically with amenorrhea and infertility. It is often thought to be an autoimmune process. Breastfeeding also reduces the rate of conception by reducing pulsatile gonadotropin secretion, resulting in lactational amenorrhea. CASE REPORT Here, we present a case of a patient with primary ovarian insufficiency. FSH and LH levels at diagnosis were in the menopausal range. After undergoing fertility treatments and failing to become pregnant, she achieved a first pregnancy with donor eggs through in vitro fertilization. After delivery, while solely breastfeeding her first baby, menses returned to normal and FSH and LH levels returned to normal. She then spontaneously conceived. She delivered a second baby without the need for assisted reproductive technology. CONCLUSIONS Pregnancy alters the maternal immune system to produce maternal-fetal tolerance through complex mechanisms that are not completely understood. The immunosuppression of pregnancy in this patient may have repressed the autoimmune process in her ovaries, allowing her to ovulate and thus reverse her primary ovarian insufficiency. Several previous case reports and studies show that immunosuppression has reduced the symptoms of primary ovarian insufficiency and allowed conception in some patients. These studies and this case report raise the question of immunosuppression as a treatment for infertility caused by primary ovarian insufficiency.

Hematological issues in critically ill patients with cancer.

Patients with solid and hematologic malignancies presenting with major bleeding or thrombotic complications, potentially life-ending events in a cancer patient's clinical course, usually require admission to an intensive care unit (ICU), making their diagnosis and management even more important for the intensivist. Given the significant advances in the diagnosis and treatment of almost all types of cancers in recent years, the intensivist is likely to encounter an ever-increasing number of cancer patients in the ICU setting with these complications. Abnormal hemostasis can occur as a consequence of both the pathology and treatment of cancer. Because cancer can have multiple effects on hemostatic equilibrium, treatment of these complications can be more complex than in the general population. This article reviews the physiology of coagulation and fibrinolysis, with special attention to those aspects that are most frequently altered in the setting of malignancy. The pathophysiology of bleeding and thrombotic complications specific to critically ill cancer patients are then detailed, and the diagnostic and therapeutic strategies are discussed. Special emphasis is placed on new cancer medications that have an effect on hemostasis, and on novel clotting and anticoagulant agents that are available to the intensivist for the management of these patients.