David Krugh

Improved nonrelapse mortality and infection rate with lower dose of antithymocyte globulin in patients undergoing reduced-intensity conditioning allogeneic transplantation for hematologic malignancies.

We sought to reduce the risk of infectious complications and nonrelapse mortality (NRM) associated with the use of antithymocyte globulin (ATG) without compromising control of acute graft-versus-host disease (aGVHD) in patients undergoing reduced-intensity conditioning (RIC) transplantation. As part of an ongoing quality improvement effort, we lowered the dose of rabbit ATG from 7.5 mg/kg of ATG (R-ATG) (n = 39) to 6.0 mg/kg of ATG (r-ATG) (n = 33) in association with fludarabine (Flu) and busulfan (BU) RIC transplantation and then monitored patients for adverse events, relapse, and survival. Of the 72 mostly high risk (82%) patients studied, 89% received unrelated donor allografts, 25% of which were HLA-mismatched. No differences in posttransplantation full donor-cell chimerism rates were observed between the 2 ATG-dose groups (P > .05). When R-ATG versus r-ATG patients were compared, we observed no significant difference in the cumulative incidence of grade II-IV aGVHD (32% versus 27%; P = .73) or grade III-IV aGVHD (23% versus 11%; P = .28). However, the r-ATG group had significantly less cytomegalovirus (CMV) reactivation (64% versus 30%; P = .005) and bacterial infections (56% versus 18%; P = .001), a better 1-year cumulative incidence of NRM (18% versus 3%; P = .03), and a trend for better 1-year overall survival (OS) (64% versus 84%; P = .07) compared to R-ATG patients. A seemingly modest reduction in the dose of rabbit ATG did not compromise control of aGVHD or achievement of donor chimerism, but led to a significant decrease in the risk of serious infections and NRM in high-risk RIC allograft recipients.

Effects of induction with novel agents versus conventional chemotherapy on mobilization and autologous stem cell transplant outcomes in multiple myeloma.

Multiple myeloma (MM) is the top indication for high-dose chemotherapy (HDC) with autologous stem cell transplantation (SCT), a strategy which improves progression-free survival and potentially overall survival (OS). Novel induction regimens incorporating the immunomodulatory (IMID) agents, such as thalidomide and lenalidomide and the proteosome inhibitor bortezomib improve response rates and survival for newly diagnosed patients. Recent data temper enthusiasm for these treatments by illustrating difficulty in some circumstances with mobilizing CD34(+) hematopoietic stem cells for subsequent HDC/SCT. We compare conventional induction regimens with novel agent-based induction strategies and the associated effects on stem cell mobilization and HDC/SCT outcome in 224 patients. Although patients exposed to novel agent inductions collected generally fewer CD34(+) cells than patients induced with chemotherapy, these differences did not translate into adverse consequences with subsequent HDC/SCT. We show that an improvement in OS after HDC/SCT may be related to induction therapy with novel agents as opposed to chemotherapy. Our data extrapolate on prior work and expand on ongoing controversies about optimal induction regimens for patients with MM planned for subsequent HDC/SCT and optimal sequencing of therapies.

Management of pregnancies complicated by anti-Fya alloimmunization

BACKGROUND: The objective was to evaluate the management and outcome of patients with anti‐Fya at the Ohio State University.

Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab

Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab

Hemolytic disease of the newborn caused by transfusion of a husband's directed blood donation. A case report.

The demand for directed blood donation in the United States is small but consistent20,21. However, with our current knowledge of alloimmunization and graft-versus-host disease, directed blood donation has been shown to have adverse effects in some recipients1,10,19. To prevent graft-versus-host disease, the Standards Committee of the American Association of Blood Banks1 now requires gamma irradiation of blood that has been donated by the blood relatives of patients. Furthermore, the latest edition of the Technical Manual of the American Association of Blood Banks advises that a woman who is planning to bear children should not receive a transfusion of red blood cells from her sexual partner or his blood relatives19. We report a case of hemolytic disease of the newborn that was caused by the transfusion of red blood cells from a husband to his wife after she had an elective total hip replacement five months before becoming pregnant. In 1990, a twenty-five-year-old woman had insertion of a non-porous-coated titanium Omniflex femoral prosthesis and a dual-geometry acetabular component (Osteonics, Allendale, New Jersey) at a large medical center in another state. Around 1992, she began to have pain in the anterior aspect of the thigh. In 1994, the patient had radiographic evidence of distal femoral osteolysis adjacent to the bullet tip of the prosthesis. She also had proximal femoral metaphyseal osteolysis and acetabular osteolysis. During November 1994, the patient donated three units of autologous blood and her husband donated one unit of directed-donor blood. At the time of the preadmission testing on November 22, 1994, the hemoglobin level was ninety-three grams per liter and the hematocrit was 27.2 percent. On December 7, 1994, the patient had excision of the old scar; complete synovectomy of the hip with removal of …