BACKGROUND: Neutrophils produce and carry key components of the alternative pathway (AP) of complement, including properdin (P). The effect of chemotherapy-induced absolute neutropenia on circulating P levels and AP function has not been previously established. METHODS: We prospectively measured free P levels in serum from 27 individuals expected to develop neutropenia after administration of chemotherapy for hematological malignancies in preparation for hematopoietic stem cell transplantation and here describe the relationship between serum P levels and the neutrophil count over time. RESULTS: When the absolute neutrophil count (ANC) was > 500 cells/mm3 pre-chemotherapy, P levels were significantly higher than P levels associated with an ANC ≤500 cells/mm3 (median values 8392 ng/mL and 6355 ng/mL, respectively; P = .001). Pairwise comparison between pre-chemotherapy P levels and P levels at initial or last documented neutropenia before recovery showed a significant decline (P < .0001). No correlation was observed between P levels during neutropenia and after recovery of neutropenia in 20 subjects for which postneutropenia samples were obtained. A small but significant (P = .02) decrease in AP hemolytic activity was noted between baseline (preneutropenia) and samples obtained at the onset of neutropenia, but only with low (6.25%) and not higher (12.5 or 25%) serum concentrations. CONCLUSIONS: A decline in P levels and AP activity could contribute to the increased risk of infection in neutropenic patients and warrants further study.

BACKGROUND: The purpose of this investigation was to: (1) determine incidence and predictors of mitoxantrone-induced early cardiotoxicity and (2) study left ventricular mechanics before and after receiving mitoxantrone. METHOD AND RESULTS: We retrospectively analyzed 80 subjects diagnosed with acute myeloid leukemia (AML) who underwent chemotherapy with bolus high-dose mitoxantrone. Echocardiographic measurements were taken at baseline and at a median interval of 55 days after receiving mitoxantrone. Thirty-five (44%) of the patients developed clinically defined early cardiotoxicity, 29 (36%) of which developed heart failure. There was a significant decrease in the ejection fraction (EF) not only in the cardiotoxicity group (17.6 +/- 14.8%, P < 0.001) but also in the noncardiotoxicity group (5.3 +/- 8.4%, P < 0.001). Decrease in global longitudinal strain (GLS) (-3.7 +/- 4.5, P < 0.001 vs. -2.4 +/- 4.3, P = 0.01) and global circumferential strain (GCS) (-5.6 +/- 9, P = 0.003 vs. -5.3 +/- 8.7, P < 0.001) was significant in both the cardiotoxicity and noncardiotoxicity group, respectively. A multivariate model including baseline left ventricular end-systolic diameter, baseline pre-E/A ratio, and baseline pre-E/e' ratio was found to be the best-fitted model for prediction of mitoxantrone-induced early clinical cardiotoxicity. CONCLUSION: High-dose mitoxantrone therapy is associated with an excellent remission rate but with a significantly increased risk of clinical and subclinical early cardiotoxicity and heart failure. Mitoxantrone-induced systolic dysfunction is evident from reduction in EF, increase in Tei index, and significant reduction in GLS and GCS. Baseline impaired ventricular relaxation evident from higher E/e' ratio and lower E/A ratio independently predicts increased risk of mitoxantrone-induced early cardiotoxicity.

BACKGROUND/AIM: Unilateral choroidal infiltration as the initial manifestation of leukemic relapse in adults is rare, particularly after an extended period of remission. This report describes this unique ophthalmic presentation, highlights the associated diagnostic challenges, and reviews the literature. METHODS: Two cases are described and an extensive literature review was conducted. RESULTS: A 59-year-old male with acute lymphoid leukemia, in remission for 18 months, presented with unilateral scleritis, exudative retinal detachment, and choroidal thickening. A 57-year-old male with a history of acute myeloid leukemia, in remission for 4 years, presented with unilateral choroidal thickening leading to secondary angle closure. In both cases, there was a significant lag from the onset of eye symptoms to establishing a systemic diagnosis of acute leukemia, leading to a delay in definitive systemic treatment, despite a high suspicion of disease based on ophthalmic findings. CONCLUSIONS: These two cases illustrate the fundus findings consistent with leukemic choroidal infiltration that can represent the first sign of relapsed leukemia. The successful treatment of these patients hinges on collaboration between ophthalmologists and oncologists to optimize patient outcomes, highlighting the need for both groups to be aware of this rare ophthalmic presentation.

Autologous hemopoietic progenitor cell (HPC) collection is the most frequent indication for an apheresis procedure in patients with multiple myeloma, up to 10% of whom may also require hemodialysis because of myeloma kidney. We investigated whether HPC collection could be performed in tandem with hemodialysis, to avoid extra outpatient visits for extracorporeal procedures, without compromising the efficacy of the hemodialysis, the HPC collection efficiency (CE) or patient safety. Four dialysis-dependent patients with multiple myeloma underwent 5 large volume leukapheresis HPC collections in tandem with hemodialysis. Under our protocol, all of the blood processed through the apheresis instrument was dialyzed against a standard calcium-rich bath prior to being returned to the patient, therefore no supplemental calcium was needed. No significant changes in pulse rate (P = 0.625) or mean arterial pressure (P = 0.188) were noted between the start and end of the procedures. The patients exhibited no signs or symptoms of hypocalcemia or other adverse effects. Calculated urea reduction ratios ranged between 62.5 and 73.9%, and HPC CE was between 53 and 84% for 4 of the 5 procedures, indicating that there was no compromise of either procedure when performed in tandem. Ionized calcium measured at the beginning, midpoint and end of every procedure did not change (P = 0.954). The two patients who proceeded to autologous HPC transplant engrafted on Days 11 and 10, respectively. We conclude that autologous HPC collection can safely be performed in tandem with hemodialysis without compromising the efficacy of dialysis, HPC CE, or patient safety.