Rosario Notaro

Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin’s lymphoma

Background:  Primary Hepatic (PHL) and Primary Splenic (PSL) non‐Hodgkin’s Lymphoma are rare entities. Small series of PHL and PSL have been reported, suggesting a non‐fortuitous association with Hepatitis C Virus (HCV) infection. The prognosis is believed to be dismal, with early recurrence and short survival.

All-trans-retinoic acid (ATRA) responsive skin relapses of acute promyelocytic leukaemia followed by ATRA-induced pseudotumour cerebri

A 30‐year‐old woman with acute promyelocytic leukaemia (APL) went into complete remission following idarubicin and cytarabine chemotherapy; 18 months later she developed repeated skin relapse, with no bone marrow involvement. DNA and RNA analysis of skin lesions revealed the presence of the PML/RARα hybrid gene, which was not detected at the same time in bone marrow. The skin relapses were successfully treated by all‐trans‐retinoic acid (ATRA) as single agent over 2 years. However, prolonged administration of ATRA caused pseudotumour cerebri, which disappeared upon drug withdrawal. The absence of the hybrid gene in the bone marrow by RT‐PCR analysis led to the patient being autografted.

PROGNOSTIC IRRELEVANCE OF CD34 IN ACUTE MYELOID LEUKAEMIA

In a recent paper by Geller et a1 (1 9 9 0 ) the expression of CD34 by blast cells of 91 patients affected by acute myeloid leukaemia (AML) ( 5 8 de novo and 33 secondary AML) was found to be significantly associated with a reduced complete remission (CR) rate. This finding was later confirmed by Guinot et a1 (1991) in a smaller series of 2 7 de novo AML. We have analysed the correlation of CD34 expression with CR rate and disease outcome in 70 de novo AML. accurately excluding other stem cell derived malignancies (secondary AML, transformed myelodysplastic syndromes, blast crisis of chronic myeloid leukaemia). The leukaemic population was considered CD34 positive if at least 15% of bone marrow blast cells reacted with the monoclonal antibodies My10 or IOM34. Such a threshold of 15% reactive cells determined, in our series, the inclusion of all differentiated leukaemias (M3) within the CD34 negative cases (P=0 .00011) , while all ’early’ leukaemias (MI and M5a) were grouped in the CD34 positive cases (P=0.00160 and 0 .00651 , respectively). M2, M4 and M5b were either CD34+ or CD34-. The chemotherapy regimen included an induction course with intermediate dose of cytarabine and an anthracycline; thereafter, all patients received a consolidation treatment (two to four courses). Patient characteristics and results are summarized in Table I. The presence of CD34 on blast cells did not

Danazol: in vitro effects on human hemopoiesis and in vivo activity in hypoplastic and myelodysplastic disorders

Abstract:  We examined the effects of danazol on in vitro growth of human bone marrow and peripheral blood progenitor cells from 15 normal donors and 5 myelodysplastic patients, and on in vivo hemopoiesis in 30 patients with hypoplastic or myelodysplastic disorders. At concentrations similar to that reported as the plasma level after oral administration, danazol significantly increased CFU‐GM colony growth in all normal donors, while the influence on CFU‐E, BFU‐E, CFU‐MK and CFU‐GEMM colony growth was less evident. The stimulatory effect on CFU‐GM was observed even after accessory cell depletion. No stimulatory effect either in vitro on the growth of all hemopoietic progenitors or in vivo was observed in 15 myelodysplastic patients, while 7 complete and 3 partial hematological responses occurred in 15 patients with hypoplastic disorders. In conclusion, our results suggest that danazol exerts a direct stimulatory activity in vitro at least on CFU‐GM, and a hemopoietic stimulatory effect in vivo in hypoplastic but not in myelodysplastic disorders.

DANAZOL FOR MYELODYSPLASTIC SYNDROMES

In a past issue of this Journal, Stadtmauer et a1 (1991) reported on the effects of danazol treatment in patients with myelodysplastic syndromes (MDS). 50% of the patients had minor clinical benefit. The authors found that MDS patients had elevated platelet associated (PAIgG) and plasma platelet bindable immunoglobulin (PBIgG), together with increased monocyte Fc gamma receptors. Danazol treatment reduced Fc gamma receptors without altering the levels of PAIgG and PBIgG. The authors concluded that danazol may modulate cytopenia by decreasing the number of Fc gamma receptors. We had a similar experience (Selleri et al. 1991). that was recently enriched by some in vitro findings, which may contribute additional data to the puzzling problem of danazol action. Our results in 47 MDS patients (18 RA; eight RA with ring sideroblasts: 14 RAEB: two RAEB-T; five CMML) treated for a minimum of 3 months with danazol (400-600 mg/d), were disappointing. A response was evident in six patients, who had platelet increase >40 x 109/1, in one case with increased WBC and in two with discontinuation of transfusion requirement (see Table I). In vitro CFU-GM colony growth, performed in methylcellulose by standard techniques (Fauser 81 Messner, 1978) in 1 5 cases, showed an increased cluster/colony ratio. No stimulatory effect on the growth following in vitro danazol addition (at a concentration similar to plasma level after oral administration of 200 mg) was observed: mean clusters: 94.7/5 x lo5 cells plated, range 10-362; mean CFU-GM: 25.7, range 1-52: clusters with danazol addition: 96.8, range 6-500; CFU-GM with danazol addition: 23.2, range 0-50). The investigation for PAIgG and PBIgG by direct and indirect immunofluorescence technique respectively (Borne et al, 1980) showed, as did Stadmauer et a1 (1991), an

Acute promyelocytic leukemia after treatment for non‐Hodgkin's lymphoma with drugs targeting topoisomerase II

We report a patient who developed acute promyelocytic leukemia (APL) concomitantly with a second relapse of non‐Hodgkins lymphoma (NHL), intermediate grade, WF type E. At diagnosis and at first NHL relapse, the patient had received the same chemotherapy regimen, which included drugs targeting DNA topoisomerase II, i.e., etoposide (total dose 5,760 mg) and idarubicin (total dose 180 mg). Thirty‐eight months after initial treatment, the patient showed pancytopenia associated with lymphoma recurrence. Bone marrow examination revealed the presence of atypical promyelocytes with Auer rods; cytogenetics showed t(15;17), and molecular analysis detected promyelocytic leukemia‐retinoic acid receptor alpha rearrangement. APL reached complete remission after all trans retinoic acid therapy, whereas NHL did not respond to further chemotherapy. In the literature, five other patients developed APL after treatment for lymphoma, from a total of 59 patients developing sAPL after treatment for any type of neoplasia. Am. J. Hematol. 60:300–304, 1999.

In vitro photoinhibition by psoralen and ultraviolet A radiation of human hematopoietic progenitors

The in vitro sensitivity of human hematopoietic progenitors to PUVA, 8‐MOP and UVA alone was investigated. 8‐MOP alone at final concentrations of 150, 200, 600 and 1000 ng/ml did not modify colony growth of circulating and bone marrow erythroid (BFU‐E), myeloid (CFU‐GM) and immature (CFU‐GEMM) hematopoietic progenitors obtained from normal controls. The exposure of the same progenitors to increasing doses of UVA, up to 12 J/cm2, progressively decreased hematopoietic colony growth (with estimated 50% inhibition occurring at about 5 J/cm2). In vitro PUVA treatment (8‐MOP 200 ng/ml followed by UVA 5 J/cm2) caused 90% growth inhibition of circulating and bone marrow hematopoietic progenitors. In addition, the treatment completely inhibited the formation of spontaneous erythroid colonies, obtained from 5 polycythemic patients, that are considered to be a marker of this neoplastic disease. PUVA cytotoxicity was assessed by the colorimetric MTT assay. The percentage of cell death after PUVA exposure was 29 ± 10% for both peripheral and bone marrow mononuclear cells. Our findings indicate that 8‐MOP alone is not toxic to hematopoietic progenitors whereas UVA treatment determines in vitro a dose‐dependent inhibition of the clonogenic capacity of normal hematopoietic cells. PUVA treatment enhances this effect, causing a quite complete inhibition of hematopoietic progenitors colony formation from normal donors and spontaneous BFU‐E colony formation from polycythemic patients.