Anna Guarini

In vivo and in vitro inhibitory effect of α-interferon on megakaryocyte colony growth in essential thrombocythaemia

Summary Megakaryocyte (MK) colony growth of bone marrow mononuclear non‐adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK‐colony forming units (CFU‐MK per 3 × 105 plated cells) was similar in ET (68 ± 33) and in controls (63 ± 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P < 0.01) greater in ET patients. Human recombinant α‐interferon 2a (α‐IFN), administered to 10 patients at a dose of 3 × 106 IU/d s.c. for 11 ± 3 weeks, was capable of inducing a significant (P < 0.01) decrease in the number (from 72 ± 16 to 31 ± 14) and size of bone marrow CFU‐MK, together with a significant reduction of the platelet count (from 1031 ± 325 to 378 ± 75 × 109/1). When added in vitro at time 0 to the culture dishes, α‐IFN inhibited the CFU‐MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that α‐IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented antiproliferative effect of this cytokine.

Acute Promyelocytic Leukemia: Results of Therapy and Analysis of 13 Cases

Acute promyelocytic leukemia (APL) was diagnosed in 13 of 84 adult patients (15.4%) with acute myeloid leukemia (AML) first admitted between 1972 and 1976. All patients had clinical and/or laboratory evidence of defibrination syndrome. Four patients died of cerebral hemorrhage within 2 days of admission. Two patients died of generalized infection on days 7, and 16, respectively, after admission. The remaining 7 patients (54%) underwent complete remission (CR) with daunomycin, arabinosyl cytosine, and adriamycin. All patients received massive platelet transfusion, no heparin, and no granulocyte transfusion. CR was more frequent in patients with a very low blast cell count and a fibrinogen level higher than 100 mg/100 ml. Median survival of these seven CR patients with APL is similar (15 months) to that of CR patients with other types of AML treated at the same institution during the same period.

The inhibitory effect of serum from hairy‐cell leukaemia patients on normal progenitor cells may disappear following prolonged treatment with α‐interferon

Summary The possibility that serum from hairy‐cell leukaemia (HCL) patients at diagnosis may show an inhibitory effect on the in vitro colony growth of normal haemopoietic progenitor cells has been suggested. Several studies have documented the efficacy of α‐Interferon (α‐IFN) in inducing a complete restoration of peripheral blood values and, in some cases, a complete clinical remission. In this study we have evaluated the regulatory effect of serum, collected before and after 3 and 12 months of a‐IFN tretment, from 10 patients with untreated HCL, on the in vitro growth of normal bone marrow CFU‐GM, BFU‐E and CFU‐MK. The effect of conditioned media, prepared from enriched hairy cells (HC) cultured in synthetic medium, on the growth of normal haemopoietic progenitors was also investigated. The results obtained confirm that sera from untreated HCL patients display a variable degree of inhibitory activity in the progenitor cell compartments analysed. Disappearance of the inhibitory activity, particularly evident for the erythroid compartment, was found only in patients who displayed a disappearance of circulating HC and a good haematological response after prolonged (12 months) treatment with a‐IFN. The possibility that the serum of patients with HCL may contain a haemopoietic inhibitory factor, released by the neoplastic HC population, is suggested.

21q− in primary thrombocythemia☆

Abstract In 11 of 18 patients with primary thrombocythemia (PT), karyotype analysis of marrow cells after Giemsa chromosome banding revealed a previously unrecognized specific abnormality, consisting in a deletion of the long arm of a chromosome #21 (21q−), del 21(q21). This deletion was observed in 11.1 to 47.6% of marrow cell metaphases. In 8 patients, 21q− cells were detected prior to any therapy. In 3 other patients, 21q− cells were found during relapse after busulfan therapy. In one patient, a translocation of the deleted material on the long arm of a #11, t(11;21)(q25;q21), was observed.

Depressed fibrinolysis in patients with acute leukaemia.

The fibrinolytic system was studied in 46 patients with acute leukaemia at diagnosis. Untreated patients (with the sole exception of the M3 subgroup) showed an inhibition of fibrinolytic activity, measured by the euglobulin lysis time and area. This inhibition was accompanied by reduced t‐PA antigen and t‐PA inhibitor activity. No correlation was found between the above‐mentioned fibrinolytic parameters and the biochemical haematological values considered, nor with clinical and/or laboratory features of DIC. fever, liver failure. The decrease in immunological plasminogen and functional α2‐antiplasmin, showed a significant correlation with the presence of clinical and/or laboratory signs of DIC, as diagnosed on the basis of concomitant increase in fibrin monomers, plasmatic fibrinopeptide A and serum FDP.

Procoagulant cellular activity (PCA) in the classification of acute leukemia

The procoagulant cellular activity (PCA) of leukemic cells was evaluated, before and after endotoxin stimulation, in 38 patients with acute leukemia at presentation subdivided according to the FAB classification. In the M4 and M5 subgroups the stimulated leukemic cells showed a significant increase in the production of PCA compared with freshly isolated cells. No evident PCA was documented in M1 and M2 AML as well as in the majority of acute lymphoid leukemias tested, both before and after endotoxin stimulation. The myeloid and lymphoid leukemic cells appear to behave similarly to normal leucocytes, within which only monocyte/macrophages are capable of producing PCA following endotoxin stimulation. These findings suggest that in human leukemic cells the endotoxin-induced production of PCA may be considered a indicator of monocyte/macrophage differentiation and thus represent a valuable diagnostic tool in the classification of acute leukemias.

Refined karyotype-based prognostic stratification of chronic lymphocytic leukemia with a low- and very-low-risk genetic profile

Refined karyotype-based prognostic stratification of chronic lymphocytic leukemia with a low- and very-low-risk genetic profile

MINIMAL RESIDUAL DISEASE (MRD) IN EARLY STAGE FOLLICULAR LYMPHOMA CAN PREDICT PROGNOSIS AND DRIVE RITUXIMAB TREATMENT AFTER RADIOTHERAPY

apies in the autoHCT cohort. There was no difference in 5 year OS between the two groups (60% vs 67%, respectively; p = 0.16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5 year OS than those without autoHCT (73% vs 60%, p = 0.02). On multivariate analysis, early use of autoHCT was associated with a significantly reduced risk of mortality (HR = 0.63, 95%CI: 0.42–0.94, p = 0.02). Conclusion: FL patients with ETF after front‐line chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in FL patients experiencing ETF.