Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders.

PURPOSE: To determine the feasibility and efficacy of pharmacokinetic (PK) -based maintenance dosing of rituximab and possibly design a more rational maintenance schedule. PATIENTS AND METHODS: Patients with CD20-positive lymphoproliferative disorders were treated with four weekly infusions of rituximab 375 mg/m(2). All patients without progressive disease were then monitored for 1 year and received a single infusion of 375 mg/m(2) when the level decreased below 25 microg/mL. RESULTS: Twenty-nine of 31 patients were assessable with a variety of histologic subtypes. The overall response rate (ORR) for the entire group was 59% with 27% complete responses (CRs) and 32% partial responses. The median PFS for all patients was 19 months, with a median follow-up of 25 months. In 22 patients with low-grade non-Hodgkin's lymphoma (LGNHL), the ORR was 63% with 36% CR and median progression-free survival (PFS) has not been reached. Of 29 assessable patients, 22 were available for PK-based maintenance. The median time to repeat bolus was 5 months (range, 1 to 9 months) for the first, 3.5 months (range, 2 to 5 months) for the second, and 3 months (range, 2 to 4 months) for the third infusion. Ninety-five percent of patients required three or fewer infusions to be maintained in the therapeutic range. CONCLUSION: Individualized PK dosing for rituximab produced efficacy comparable to other published maintenance strategies. PK data from this trial suggest that a rational maintenance strategy in patients with LGNHL would be a single dose of 375 mg/m(2) of rituximab every 3 to 4 months.

Benign B-cell precursors (hematogones) are the predominant lymphoid population in the bone marrow of preterm infants.

Bone marrow (BM) findings in 3rd-trimester stillborns and full-term living neonates have been previously described. However, there is no information regarding BM composition in living preterm infants. Specifically, it is unknown whether the BM lymphocytosis seen in full-term infants at 1-4 weeks of age also occurs in preterm infants. Furthermore, the lineage of these cells has never been investigated. We used a panel of immunohistochemical stains to characterize the BM composition in 11 neonates (8 living and 3 deceased). Unlike in the other age groups, immature B cells (hematogones) were the most common lymphoid population, accounting for 10-60% (mean 34%) of all cells. In two additional cases (both living patients), flow cytometry revealed a level of 3.8% of immature B cells in a <1-week-old neonate and 25.7% in a 19-week-old infant. Immature B cells were not identified in 6 peripheral blood samples from preterm neonates. These findings are pertinent for the interpretation of BM and peripheral blood samples in this age group as survival improves and diagnostic samples become more common.

Hodgkin's lymphoma after post-transplant lymphoproliferative disease in a renal transplant recipient.

Lymphoid malignancies such as post-transplant lymphoproliferative disease (PTLD) are a major complication of solid organ transplantation. Hodgkin's lymphoma (HL) is not part of the typical spectrum of PTLD, but has rarely been reported as a separate complication. We report a case of HL occurring after previous PTLD in a renal transplant recipient. A 9-yr-old girl with end-stage autosomal recessive polycystic kidney disease received a cadaveric renal transplant at 1 yr of age. She developed polymorphic PTLD localized to the bone marrow at 6 yr post-transplant. She was treated with reduction of immunosuppression and alpha-interferon. No chemotherapy or anti-B cell antibody was administered. The PTLD resolved and kidney graft function remained stable. At 9 yr post-transplant, she presented again with fever of 2 wk duration, associated with enlarged lymph nodes at multiple sites. A lymph node biopsy revealed the presence of classic Reed Sternberg cells positive for CD15, CD30 and EB RNA. She was treated with standard combination chemotherapy for HL with COPP/ABV. All immunosuppressive agents were discontinued except for low dose prednisone. The patient had an excellent response, with resolution of her lymphadenopathy and maintenance of stable graft function. RS like cells have been reported in the setting of PTLD, but these cells possess an activated B cell phenotype, are EBV negative and CD15 negative. True HL following PTLD has been reported in only three previous cases, with good response to standard chemotherapy in each.

Granulocytic sarcoma (chloroma) of the breast: a diagnostic dilemma and review of the literature.

Primary granulocytic sarcoma (GS) is a rare entity, and even more unusual is the presence of primary GS of the breast. We describe such a case and report on the 19 cases of primary breast GS in the literature. Primary GS presents most commonly in skin and lymph nodes, therefore when it presents in the breast, misdiagnosis is a common problem. Primary breast GS is misdiagnosed most frequently as lymphoma or sarcoma. Histologic testing and immunostains are essential to provide the proper diagnosis. It appears that early initiation of systemic acute myelogenous leukemia (AML)-type chemotherapy is beneficial and may delay or avert the development of AML in bone marrow and blood.

Thrombopoietin administered during induction chemotherapy to patients with acute myeloid leukemia induces transient morphologic changes that may resemble chronic myeloproliferative disorders.

Thrombopoietin (TPO), a potent stimulator of megakaryocyte and platelet production, has been used in clinical trials to reduce thrombocytopenia after chemotherapy in patients with acute myeloid leukemia (AML). We report that TPO therapy is associated with peripheral blood and bone marrow findings that can mimic myeloproliferative disorders. Peripheral blood and bone marrow samples of 13 patients with AML who received TPO were examined. A subset of bone marrow samples exhibited hypercellularity, megakaryocytic hyperplasia, and reticulin fibrosis after TPO administration. Cases demonstrated as many as 58.4 megakaryocytes per high-powerfield (MHPF) compared with 3.7 MHPF in the control group. Megakaryocytic atypia, increased mitoses, emperipolesis, intrasinusoidal megakaryocytes, and thickened trabeculae also were seen. Peripheral blood findings included leukoerythroblastosis, leukocytosis, thrombocytosis, and circulating megakaryocyte nuclei. Changes resolved within 3 months after discontinuation of TPO. This rapid resolution of the morphologic abnormalities induced by TPO distinguishes these findings from those seen in true chronic myeloproliferative disorders.