Primary bone lymphoma (PBL) is a rare extranodal presentation within lymphomas and primary bone malignancies. Pathologic fracture (PF) is a common complication of metastatic bone disease but is, rarely, the presentation of a primary bone tumor. We report a case of an 83-year-old man with a history of untreated prostate cancer, presenting with atraumatic fracture of his left femur after months of intermittent pains and weight loss. Radiographic workup revealed a lytic lesion suspicious for PF secondary to metastatic prostate cancer; however, initial core biopsy results were inconclusive for malignancy. A complete blood count with differential and complete metabolic panel was within normal limits. During surgical fixation and nailing of the femur, a reaming biopsy was performed as a repeat measure and revealed diffuse large B-cell lymphoma. Staging with positron emission tomography and computed tomography found no evidence of lymphatic or visceral involvement and chemotherapy was promptly initiated. This case highlights the diagnostic workup challenges for PF secondary to PBL, especially in the setting of concurrent malignancy. Because of the non-specific presentation of a lytic lesion on imaging associated with atraumatic fracture, we highlight PBL as an important diagnostic consideration.

The use of Rho(D) immune globulin in Rh-negative pregnant women has become standard of care, but many practicing clinicians do not know the dosing recommendations for this essential medication. In this article, we describe a case of a 15-year-old girl who presented with intrauterine fetal demise and was found to have massive fetomaternal hemorrhage. Kleihauer-Betke testing results indicated nearly 460 mL of fetal blood in the maternal circulation. The patient ultimately received 4800 µg of Rho(D) immune globulin, a dose that required close coordination with the obstetrical service and pharmacy. Although this is an unusual case of large-volume, potentially chronic, fetomaternal hemorrhage, it is also an excellent illustration of the principles for diagnosing this condition, as well as providing dosing guidelines for Rho(D) immunoglobulin to prevent alloimmunization.

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Introduction: Ibrutinib, a Bruton's tyrosine kinase inhibitor, has been approved for the treatment of many hematological malignancies including but not limited to, chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma, and marginal zone lymphoma. Despite the efficacy of this drug in the treatment of hematologic diseases, multiple adverse effects have been well reported. This study seeks to present a combined analysis of currently available randomized controlled trials (RCTs) on the incidence of high-grade hematological toxicities and hypertension, in patients being treated with ibrutinib for hematological malignancies. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing ibrutinib in patients with hematologic malignancies that mention high-grade hematological toxicities and hypertension were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Random effects model was applied. Results: A total of 3,920 patients with CLL/SLL, mantle-cell lymphoma, Waldenstrom's macroglobulinemia and diffuse large b-cell lymphoma, from 10 phase III RCTs were eligible. Studies compared ibrutinib+ obinutuzumab vs chlorambucil+ obinutuzumab, ibrutinib vs chlorambucil, bendamustine+ rituximab vs ibrutinib vs ibrutinib+ rituximab, ibrutinib+ rituximab vs fludarabine+ cyclophosphamide+ rituximab, ibrutinib vs rituximab, ibrutinib vs ofatumumab, ibrutinib+ bendamustine+ rituximab vs bendamustine+ rituximab, ibrutinib vs temsirolimus, ibrutinib+ rituximab+ cyclophosphamide+ doxorubicin+ vincristine+ prednisone vs rituximab+ cyclophosphamide+ doxorubicin+ vincristine+ prednisone were included in the analysis. The randomization ratio was 2:1 in E1912 study and Huang et al study and 1:1 in other studies. The I2 statistic for heterogeneity was 32, suggesting some heterogeneity among RCT. The RR of high-grade hematologic side effects were as follows: anemia, 0.60 (95% CI: 0.36 - 1.02; p = 0.06); neutropenia, 0.76 (95% CI: 0.55 - 1.05; p = 0.10); thrombocytopenia, 0.69 (95% CI: 0.35 - 1.37; p = 0.29); and febrile neutropenia, 0.65 (95% CI: 0.30 - 1.42; p = 0.29). The incidence of high-grade hypertension (HTN) was 187 (8.59%) in study group vs 40 (2.29%) in control group with RR of 2.51 (95% CI: 1.64 -3.85; P < 0.0001). In a subset of patients with CLL/SLL treated with ibrutinib (n= 2658), the RR of high-grade hematologic side effects were as follows: anemia, 0.51 (95% CI: 0.35 - 0.74; p = 0.0005); neutropenia, 0.73 (95% CI: 0.52 - 1.01; p = 0.06); thrombocytopenia, 0.72 (95% CI: 0.38 - 1.39; p = 0.33); and febrile neutropenia, 0.54 (95% CI: 0.22 - 1.37; p = 0.20). High-grade HTN rate was 8.11% higher in ibrutinib group compared to control arm (RR, 2.49; 95% CI: 1.47 - 4.22; P = 0.0007). Conclusions: This literature review determined that ibrutinib's efficacy must be carefully balanced against the mentioned side effects on a case by case basis. Of special consideration is the rate of HTN in the Ibrutinib group compared to the control. These findings need to be further explored to determine the efficacy of Ibrutinib in specific patient populations with varying underlying diseases. Disclosures No relevant conflicts of interest to declare.