Phase I trial of low-dose oral Clofarabine in myelodysplastic syndromes patients who have failed frontline therapy.

We investigated protracted low-dose oral Clofarabine for the treatment of myelodysplastic syndromes (MDS). Adults with an International Prognostic Scoring System (IPSS) score of INT-1 or higher who had failed first line therapy were eligible. INT-1 patients had to be transfusion-dependent. We started with oral Clofarabine at 5mg (fixed dose) daily for 10 consecutive days on a 28-day cycle. Toxicity prompted a modification to 1mg PO daily for 10 days and then 1mg PO daily for 7 days. Patients received treatment indefinitely until loss of response or unacceptable toxicity. Nine patients (5 women) were enrolled and evaluable (median age 65 years; range 55-81). A 10-day regimen of oral Clofarabine at 5mg/day induced Grade IV pancytopenia. A dose of 1 mg/day for 7/28 days was very well tolerated without significant toxicity. Three patients had responses (2 with responses lasting up to 21 and 51 cycles) defined as stable disease in spite of no significant change on bone marrow evaluation. Low-dose oral Clofarabine (1mg daily for 7/28 days) proved both effective and safe for patients with MDS who had failed prior therapy. This patient population is particularly sensitive to more protracted Clofarabine treatment schedules.

Early diagnosis of intravascular large B-cell lymphoma: clues from routine blood smear morphologic findings.

Intravascular large B-cell lymphoma (IVLBCL) is a mature B-cell neoplasm characterized by malignant lymphoid cells within the lumina of blood vessels and capillaries. Given its varied and nonspecific clinical manifestation, this aggressive disease is often not diagnosed until an advanced clinical stage or even at autopsy. This case highlights a patient presenting with autoimmune hemolytic anemia (AIHA) and fevers. Atypical circulating cells on a screening peripheral smear lead to flow cytometric studies highlighting an increase in large, light chain restricted CD20 positive cells. A diagnostic bone marrow biopsy was performed and trephine cores demonstrated predominantly intrasinusoidal lymphoma cells. In conjunction with additional immunophenotypic data, these studies strongly supported a diagnosis of IVLBCL. Judicious use of flow cytometry and morphology resulted in an early-stage diagnosis and likely contributed to the patient's current complete remission status following anti-CD20 therapy. Differential diagnoses for this presentation are discussed in light of serologic, immunophenotypic, histologic, and cytogenetic findings.