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A rare cause of a spontaneous, life threatening coagulopathy in adults is the development of autoantibodies to factor VIII. We recently had the opportunity to treat seven patients with this disorder. After stabilization, they were given a regimen consisting of prednisone and oral cyclophosphamide. All patients had a complete response to treatment. The median time to response was three weeks. Durable remissions were achieved, making this oral regimen an acceptable treatment for this disorder. Am. J. Hematol. 60:70-71, 1999.

Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy, thus consolidation with hematopoietic cell transplantation (HCT) has been used with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel, targeted therapy of CLL/SLL. We performed a CIBMTR registry study evaluating outcomes after autologous (auto, n=53) and allogeneic (allo, n=118) HCT in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response at HCT relative to allo-HCT recipients (66% versus 34%), while a higher proportion of allo-HCT recipients had 17p deletion (33% versus 7%) and had previously received novel agents (39% versus 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3y PFS/OS: 66%/77% CR versus 43%/57% PR versus 5%/15% resistant, p<.0001 for both), while cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.

The B-1 B cell population is an important bridge between innate and adaptive immunity primarily because B-1 cells produce natural antibody. Murine B-1 and B-2 cells arise from distinct progenitors. In humans, however, partly because it has been difficult to discriminate between them phenotypically, efforts to pinpoint the developmental origins of human B-1 and B-2 cells have lagged. To characterize progenitors of human B-1 and B-2 cells, we separated cord blood and bone marrow Lin−CD34+ hematopoietic stem cells (HSC) into Lin−CD34+CD38lo and Lin−CD34+CD38hi populations. We found that transplanted Lin−CD34+CD38lo cells but not Lin−CD34+CD38hi cells generated a CD19+ B cell population after transfer into immuno-deficient NOD.Cg-Prkdcscid Il2rgtm1wjl/SxJ neonates. The emergent CD19+ B cell population was found in spleen, bone marrow, and peritoneal cavity of humanized mice, and included distinct populations displaying the B-1 or the B-2 phenotype. Engrafted splenic B-1 cells exhibited a mature phenotype as evidenced by low-to-intermediate CD24 and CD38 expression levels. The engrafted B-1 cell population expressed a VH-DH-JH composition similar to cord blood B-1 cells, including frequent use of VH4-34 (8% versus 10%, respectively). Among patients with hematologic malignancies undergoing HSC transplantation, B-1 cells were found in the circulation as early as 8 weeks post-transplantation. Altogether, our data demonstrate that human B-1 and B-2 cells develop from a Lin−CD34+CD38lo stem cell population, and engrafted B-1 cells in humanized mice exhibit an immunoglobulin usage pattern comparable to B-1 cells in cord blood.

Purpose of review Acute kidney injury (AKI) in the setting of hematopoietic stem cell transplantation (HSCT) is common in pediatric and adult patients. The incidence ranges from 12 to 66%, and development of AKI in the posttransplant course is independently associated with higher mortality. Recent findings Patients who undergo HSCT have many risk factors for developing AKI, including sepsis, use of nephrotoxic medications, graft versus host disease (GVHD), and veno-occlusive disease (VOD). In addition, engraftment syndrome/cytokine storm, transplant-associated thrombotic microangiopathy (TA-TMA), and less common infections with specific renal manifestations, such as BK and adenovirus nephritis, may lead to kidney injury. There has been significant advancement in the understanding of TA-TMA in particular, especially the role of the complement system in its pathophysiology. The role of early dialysis has been explored in the pediatric population, but not well studied in adult HSCT recipients Summary This review provides an update on the risk factors, causes, and treatment approaches to HSCT-associated AKI. Video abstract http://links.lww.com/COCC/A29

Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD 19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation. With a median follow-up time for patients of 5.8 years, the median event-free survival for protocol treatment and observation are 2.1 and 2.9 years, respectively (p = 0.275). The median overall survival for treatment and observation are 6.1 years and not reached, respectively (p = 0.063). Therefore, no differences were found in event-free survival and overall survival between protocol treatment and observation, although there was a trend toward improved survival with observation. These data fail to support a role for anti-B4-bR as consolidative therapy after bone marrow transplant in patients with B-cell lymphoma.

The objective of this work was to determine the safety and efficacy of gemtuzumab ozogamicin in patients with poor prognosis acute myeloid leukemia (AML). Patients with the following diagnoses/characteristics were treated with 1-3 infusions of gemtuzumab ozogamicin at a dose of 9 mg/m2: (1) relapse of AML < or = 6 months of first complete remission (CR); (2) AML refractory to chemotherapy at initial induction or at first relapse; (3) AML in second or greater relapse; (4) myeloid blast crisis of chronic myeloid leukemia (CML); (5) untreated patients > or = 70 years or > or = 55 years with abnormal cytogenetics (excluding inv 16, t(15;17) and t(8;21)) and/or an antecedent hematologic disorder; (6) refractory anemia with excess blasts in transformation (RAEBT). Forty-three patients, ages 19-84 (mean 62), were treated, including 7 patients with untreated AML age > 70 years, 2 with untreated RAEBT, 14 with AML first salvage (first remission 0-6 months), 15 with AML > or = second salvage and 14 with myeloid blast phase of CML. The overall response rate was 14%, with 4/43 (9%) patients achieving CR and 2/43 (5%) achieving CR without platelet recovery. The most significant toxicity was neutropenic fever, which occurred in 84% of patients. In conclusion, in patients with relapsed/refractory AML, gemtuzumab ozogamicin has a comparable response rate to single-agent chemotherapy and may offer a more favorable toxicity profile.