Malignant syphilis or lues maligna is a severe form of secondary syphilis that was commonly reported in the pre-antibiotic era, and has now reemerged with the advent of the human immunodeficiency virus (HIV) epidemic. However, the characteristic histopathological findings of malignant syphilis remain controversial. The aim of this case report was to clarify the clinical and histopathological findings of HIV-positive malignant secondary syphilis. A Japanese man in his forties complained of fever, skin lesions, headache, and myalgia without lymphadenopathy during the previous 4 weeks. The skin lesions manifested as erythematous, nonhealing, ulcerated papules scattered on his trunk, extremities, palm, and face. Although the skin lesions were suspected to be cutaneous T-cell lymphomas on histological analyses, they lacked T-cell receptor Jγ rearrangement; moreover, immunohistochemical analyses confirmed the presence of spirochetes. The patient was administered antibiotics and anti-retroviral therapy, which dramatically improved the symptoms. On the basis of these observations of the skin lesions, we finally diagnosed the patient with HIV-associated secondary syphilis that mimicked cutaneous T-cell lymphoma. The patient’s systemic CD4+ lymphocyte count was very low, and the infiltrate was almost exclusively composed of CD8+ atypical lymphocytes; therefore, the condition was easily misdiagnosed as cutaneous lymphoma. Although the abundance of plasma cells is a good indicator of malignant syphilis on skin histological analyses, in some cases, the plasma cell count may be very low. Therefore, a diagnosis of malignant secondary syphilis should be considered before making a diagnosis of primary cutaneous peripheral T-cell lymphoma or lymphoma associated with HIV infection.

SUMMARYThe inhibiting activity of serum on haematopoiesis has been described in patienis with SLE. To explore further the features of serum inhibitor, we first examined the suppression of granulocytic and erythroid colony formation in vitro by serum from palients with SLE using methylcellulose culture. The potent inhibiting activity was demonstrated in six of 20 patients. All of these six patienis were associated with leukocytopenia and/or anaemia. Five of 10 sera from patients with active SLE suppressed the colony formation of both burst-forming units of erythrocyte (BFU-E) and colony-forming units of granulocyte/niaerophage (CFU GM). and one serum suppressed BFU-E only, IgG fraction isolated from sera with inhibiting activity suppressed colony formation without complement involvement. The elimination of monocytes and lymphocytes from target mononuelear cells did not affect Ihe suppression by the IgG fractions. The suppressive effect was completely eliminated after incubation ofthe IgG fractions with progenitor-enriched mononuclear cells. Flow cytometric analysis showed these igG bound to CD34' haematopoietic progenitor cells, but not to CD33^ cells. These data suggest that (i) the inhibitor of colony formation in serum was observed in IgG fraction; (ii) its suppressive efTect on colony formation was mediated by neither monocytes and lymphocytes nor complements; and (iii) IgG fraction could bind to primitive haematopoietie progenitor cells and suppress the growth of these cells. Thus. IgG autoantibodies to primitive haematopoietic progenitor eells are demonstrated to be present in the sera ofa significant proportion of active SLE patients with anaemia and leukocytopenia and to suppress the progenitor cell growth.

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Platelet-derived growth factor (PDGF) and other cytokines released from megakaryocytes are thought to play a crucial role in the pathogenesis of myelofibrosis. We describe a patient with essential thrombocythaemia (ET) who developed myelofibrosis with an increased level of serum thrombopoietin (TPO). Recombinant human (rh) TPO stimulated the proliferation and spontaneous megakaryocyte colony formation of the neoplastic cells in the peripheral blood. Moreover, serum concentrations of PDGF, platelet factor 4, and beta-thromboglobulin were elevated and the production of these growth factors from the megakaryocyte progenitors was augmented with the addition of rhTPO in vitro. These results indicate that TPO may contribute to the development of myelofibrosis in ET.

1532 The current standard initial treatment for APL is all-trans retinoic acid (ATRA) and anthracycline with or without citarabine, followed by ATRA maintenance. Although the treatment has greatly improved clinical outcomes of APL, a considerable proportion of patients still undergo disease relapse, requiring salvage therapy with such as arsenic trioxide (ATO). GO, an anti-CD33 monoclonal antibody conjugated with calicheamicin, is also highly effective on APL. Highly homogeneous expression of CD33, potential efficacy of calicheamicin and lower expression of P-glycoprotein on APL cells explain the high potency of GO on APL. We report here on the efficacy of GO monotherapy against relapsed/refractory APL in a post-marketing surveillance study of GO in Japan. All patients who were treated with GO alone were obligatorily registered into a post-marketing surveillance study run by Wyeth Japan, Co. Ltd. under the guidance of the Pharmaceutical and Medical Devices Agency. We obtained permission to access patients' data from each institution and Pfizer Japan, Co. Ltd. The survey items included adverse events, treatment outcome, overall survival (OS) and relapse-free survival (RFS). Clinical and biological characteristics were analyzed in APL and compared by chi-square test or Fisher's exact test for categorical data, and Wilcoxon rank-sum test for continuous data. OS and RFS were estimated by the Kaplan-Meier method in APL, and then compared to those from the simultaneous post-marketing study in acute myeloid leukemia (AML) by the log-rank test. Between 2005 and 2008, 27 relapsed/refractory APL patients were enrolled in this surveillance. Of these, two patients were excluded from analysis because of insufficient data, while 726 AML patients were enrolled and 503 were evaluable. Twelve (48%) and 2 (9%) APL patients who were treated with GO alone achieved CR and CRp, respectively, while 42 (8%) and 41 (8%) of AML achieved CR and CRp, respectively. Remission duration of first CR and number of relapses influenced CR rates, but previous usage of ATO and age did not in APL. OS and RFS at 2 years were 63% and 71% in APL, and 14% and 20% in AML, respectively. These were shown in figures. OS and RFS in APL were better than those in AML (P<0.0001 and P=0.0074, respectively). Treatment related adverse events of GO (grade 3 or 4) in APL patients were infection (24%), bleeding (8%), lung damage (4%) and reversible veno-occlusive disease (4%); these were similar in AML patients. Although other previous clinical studies failed to confirm clinical benefit of GO on AML, single use of GO is highly effective and relatively safe in relapsed/refractory APL. The efficacy was also observed in elderly patients and in relapsed ones after ATO therapy. Further studies are warranted, in which GO is included in addition to ATRA and ATO in the treatment of high-risk APL. Disclosures: Takeshita: Novartis Pharma: Research Funding; Takeda Pharma: Research Funding. Naoe:Kyowa-Hakko Kirin.: Research Funding; Dainipponn-Sumitomo Pharma.: Research Funding; Chugai Pharma.: Research Funding; Novartis Pharma.: Honoraria, Speakers Bureau; Zenyaku-Kogyo: Research Funding; Otsuka Pharma.: Research Funding.