Paul F. Galbraith

Aplastic anemia following administration of a tumor necrosis factor‐α inhibitor

Abstract: Upregulation of tumor necrosis factor‐alpha (TNF‐α) has been implicated in the pathogenesis of several inflammatory conditions, including rheumatoid arthritis. Therapeutic agents such as antibodies or soluble TNF‐α receptor analogs, which block TNF‐α activity are a recent addition to the therapeutic armamentarium for the conditions. We describe a patient who developed aplastic anemia complicated by sepsis after receiving etanercept, a TNF‐α receptor analog, for the treatment of rheumatoid arthritis. Pancytopenia resolved within 3 wk of discontinuing etanercept. To our knowledge, this is the first report of aplastic anemia associated with TNF‐α blockade.

Clinical progression and outcome of patients with monoclonal B-cell lymphocytosis.

Monoclonal B-cell lymphocytosis (MBL) is a clonal lymphoproliferation with the immunophenotype of chronic lymphocytic leukemia (CLL) but a B-lymphocyte count of less than 5 × 109/l and no lymphadenopathy, organomegaly, cytopenias or symptoms. We performed a retrospective analysis of patients with MBL (n = 46), Rai stage 0 CLL (n = 112) and Rai stage ≥1 CLL (n = 54). Median follow-up and range was 30 (0.1 – 120) months for MBL, 60 (0.1 – 309) months for stage 0 CLL and 54 (0.1 – 309) months for stage ≥1 CLL. None of the MBL patients required treatment compared with 24 of 112 (21%) stage 0 CLL and 28 of 54 (52%) stage ≥1 CLL patients (p < 0.0003). No MBL underwent aggressive transformation compared with 1 of 112 (0.8%) stage 0 CLL and 6 of 54 (11%) stage ≥1 CLL patients (p < 0.0003). Progression-free survival (PFS) appeared improved in MBL compared to stage 0 CLL, although this did not reach statistical significant (p = 0.07) due to the relatively short follow-up in the MBL group; two year PFS was 97.2% for MBL, 93.1% for stage 0 CLL, and 68% for stage ≥1 CLL patients (p < 0.0001 for stage ≥1 CLL compared with MBL and stage 0 CLL). This is the first study of outcome in MBL which demonstrates that patients have an improved disease course compared to stage 0 CLL patients. Over a median 2.5 years of follow-up, no MBL patients required treatment or died of CLL-related causes.

Improved outcome of human immunodeficiency virus-associated plasmablastic lymphoma of the oral cavity in the era of highly active antiretroviral therapy: a report of two cases.

Plasmablastic lymphoma (PBL) is a recently described type of non-Hodgkins lymphoma (NHL) that occurs in up to 3% of patients with HIV infection. Although the clinical-pathological features of several patients with HIV-associated plasmablastic lymphoma are documented, detailed description of clinical outcome is limited to isolated case reports. Generally, the response to lymphoma therapy is poor and survival is short. Response to highly active anti-retroviral therapy (HAART), however, has also been described. In this report, we describe the clinical course of two patients diagnosed with HIV-associated PBL in the era of HAART. One patient had a complete response to HAART, with a response-duration of 14 months, followed by relapse in the gastrointestinal tract several months after an anti-retroviral holiday. He is currently in complete remission (CR) eight months from diagnosis of relapse after receiving a full course of combination chemotherapy with modified CHOP, and 25 months from initial diagnosis. A second patient responded to brief chemotherapy in conjunction with HAART and is in clinical CR ten months from diagnosis. These cases illustrate that immunologic and virologic control with HAART may be beneficial for treating PBL and may possibly maintain continued CR. We advocate a high index of suspicion for primary PBL or its recurrence in patients with HIV infection, a history of low CD4 counts or high viral load, and oral or gastrointestinal symptoms.

Improved Survival in HIV-Associated Diffuse Large B-Cell Lymphoma with the Addition of Rituximab to Chemotherapy in Patients Receiving Highly Active Antiretroviral Therapy

Abstract Purpose: Recent trials suggest serious toxicity in HIV-associated non-Hodgkin’s lymphoma (NHL) with rituximab (R) and chemotherapy (CT), offsetting the benefit of rituximab. Method: We retrospectively reviewed experience with CHOP-R vs. CT in 40 patients with HIV-associated diffuse large B-cell lymphoma (DLBCL) diagnosed between December 1992 and February 2006, all of whom were treated with curative intent. Results: In a univariate analysis, International Prognostic Index (IPI) score, prior AIDS, HAART, and rituximab were significant for overall survival (OS). In a multivariate analysis, IPI 0-1 (p < .02), no prior AIDS (p < .0002), and receiving CHOP-R (p < .01) were significant for improved OS, and HAART use (p < .09) retained a trend for improved OS. The hazard ratio (HR) for patients with high IPI receiving CHOP-R was 0.3 (95% CI 0.1-0.8). Patients without prior AIDS receiving CHOP-R had an HR of 0.5 (95% CI 0.1-1.7). The OS at 30 months in patients not receiving HAART was 0%. With HAART, OS was 33% for CT and 86% for CHOP-R; HR for CHOP-R was 0.4 (95% CI 0.1-1.2). Toxic deaths were 3 (33%) for CHOP-R and 6 (25%) for CT (p = ns); all toxic deaths with CHOP-R were in patients not receiving HAART. Rituximab-treated patients had a lower death rate from lymphoma (CHOP-R, 2 [16%] vs. CT, 15 [63%]; p < .04), and overall mortality (CHOP-R, 5 [42%] vs. CT, 21 [88%]; p < .01). Conclusion: These retrospective data suggest that fatal toxicity of rituximab in HIV-NHL is not increased provided HAART is used, that the addition of rituximab to CT improved outcome, and that further prospective trials investigating this issue are warranted.

Case report: A patient with primary biliary cirrhosis and autoimmune haemolytic anaemia

Diseases of an autoimmune nature are well recognized in association with primary biliary cirrhosis. Although autoimmune thyroiditis and many rheumatological conditions are well described in primary biliary cirrhosis, autoimmune haematological diseases have been less well reported. We report on a 66 year old North American Indian man with coincident primary biliary cirrhosis and warm antibody haemolytic anaemia. This case report supports the suggestion of an association between autoimmune haemolytic anaemia and primary biliary cirrhosis.

Acute Leukemia in Patients Sixty Years of Age and Older : A Twenty Year Single Institution Review

Objectives:Acute leukemia, particularly acute myeloid leukemia, occurs more frequently in the elderly, a growing segment of the North American population. To evaluate our progress in the diagnosis, treatment and outcome of this condition, we reviewed our experience of all patients ≥60 years of age diagnosed with acute leukemia over a 20-year period at Saint Pauls Hospital, a university-based hospital in Vancouver, Canada. Methods:A retrospective chart review was performed of 103 patients ≥60 years of age diagnosed with acute leukemia (acute myeloid leukemia-81; acute lymphoid leukemia-15; acute leukemia not otherwise specified-7). Results:Median age was 72 (range 60–88) years. Bone marrow aspirate yielded cytogenetic information on 57 patients and 18 (31.6%) had an unfavourable karyotype. Fifty-three (51%) patients received induction chemotherapy (treated) and 50 (49%) were palliated (untreated). Treated patients were younger [median 67 years (range 60–79)] than untreated patients [76 years (61–88)], (P < 0.0001). Of the treated patients, 33 (62%) achieved a complete remission. The median overall survival for the group was 104 (1–2689) days, and for treated versus untreated patients-219 (1–2689) and 39 (2–1229) days, respectively (P = 0.0021). Univariate variables predictive of prolonged survival included induction chemotherapy (P = 0.0027), de novo leukemia (P = 0.0420), and younger age, with a relative increase in death in older subgroups (60–69, 70–79, 80+), (P = 0.0311). Induction chemotherapy was the only predictor of prolonged survival in multivariate analysis (P = 0.0027). Conclusions:The prognosis of acute leukemia in older patients remains poor, and even though induction chemotherapy seem to prolong survival in patients able to receive treatment, most ultimately die of leukemia.