James D. Cotelingam

Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSEnThis phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS).nnnPATIENTS AND METHODSnThirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated.nnnRESULTSnFour patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis.nnnCONCLUSIONnThe combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.

Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSEnThis phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS).nnnPATIENTS AND METHODSnForty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment.nnnRESULTSnTwo patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia.nnnCONCLUSIONnThese results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

Comparative utility of diagnostic bone-marrow components : A 10-year study

Ten years of cumulative experience represented by 4,902 consecutive diagnostic bone‐marrow examinations at a tertiary care and referral center were reviewed to assess the value of specific components. While it has been shown previously that the information obtained from each component is generally complementary, the inclusion of some or all components may vary between institutions. The components studied included aspirate smears, clot sections, biopsy cores, and touch imprints of biopsy and clot sections. Three clinical presentations accounted for the majority of cases: staging for carcinoma or lymphoma, cytopenias, and acute leukemia. We conclude that bilateral aspirates with biopsies are required for diagnosis in staging of neoplasms and that a unilateral aspirate with biopsy is sufficient to assess patients with cytopenia or leukemia. Only rarely were touch imprints of biopsy cores necessary to establish a diagnosis; however, their early availability prior to examining sections of the clot and core did provide immediate information, when positive, in the staging of patients with carcinoma. In a small percentage of staging and leukemia cases the diagnosis rested with the clot section alone. The findings in this study address common assumptions associated with routine diagnostic hematology and oncology procedures, and are important to both clinicians and pathologists concerned with accuracy, quality assurance, turnaround time, and cost containment. Am. J. Hematol. 56:37–41, 1997.

Prognostic implications of a bone marrow histopathologic classification system in mycosis fungoides and the Sézary syndrome

Background. The authors devised a histopathologic classification system for interpreting bone marrow biopsy materials in patients with mycosis fungoides and the Sézary syndrome and correlated histopathologic findings with clinical stage and outcome.

Whole-body pathologic analysis of a patient with thorotrast-induced myelodysplasia. Comment

An autopsy was performed on a 72-y-old Caucasian female who had received a carotid artery injection of thorium dioxide in 1953. The body was dissected in such a manner as to provide for radiobiological evaluation as well as to determine histologically the distribution of Thorotrast in the tissues and its complications. Thorotrast was identified within the liver, spleen, lymph nodes, bone marrow, and surrounding the right carotid artery (the injection site). The cause of death was gastric hemorrhage complicating pancytopenia secondary to refractory anemia with excess of blasts (myelodysplastic syndrome).