Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytaBOM) for patients with intermediate or high grade non-Hodgkin lymphomas (G, H and K according to the Working Formulation), was tested by the Gruppo Cooperative Lombardo to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimen in a cooperative group setting. Among 64 previously untreated patients, aged between 20 and 71 years, 7 had stage IB-IIB, 12 had stage IIIA-B, 45 (67%) had stage IVA-B. There were 44 complete remissions (CRs) (69%) and 14 partial remissions (22%); the difference between patients in stage I-II-III (84% complete remissions) and those in stage IV (62% complete remissions) was statistically significant. The median length of follow up was 20 months (range 1-60 months), with 56% of patients alive at 60 months and 53% of CRs patients free of disease at 60 months. Patients in stage I-II-III have the best survival and disease free survival compared to stage IV, 87% versus 42% and 72% versus 32% respectively (both with high statistical significance). Grade 3-4 (WHO) haematological toxicity was observed in 39% of patients, with 3 septic deaths. Two more patients died with chemotherapy related toxicity (1 stroke and 1 acute renal insufficiency). Administration of ProMACE-CytaBOM is a feasible and safe regimen although it presents moderate toxicity. ProMACE-CytaBOM may represent improved treatment for aggressive lymphomas, in terms of duration of response and survival, but a longer follow up is needed.

BACKGROUND AND OBJECTIVE:Hepatic toxicity directly related to the drugs administered in cyclic chemotherapy (CT), although sometimes serious, does not limit the treatment of non-Hodgkin's lymphoma (NHL). Nevertheless, reports of reactivation of viral hepatitis in NHL patients with B virus (HBV) infection are becoming more frequent. The recent observation of two cases of severe liver toxicity directly correlated to CT and a case of fatal hepatic failure due to HBV replication prompted us to evaluate the hepatic toxicity of CT in 98 consecutive B-cell NHL patients treated with relatively homogeneous cyclic CT. METHODS:Acute hepatic toxicity was retrospectively evaluated in 98 consecutive B-cell NHL patients who received induction CT. HBV and HCV markers were checked at presentation. All patients were tested for ALT and bilirubin before every CT course, while tests for HBV-DNA and/or for HCV-RNA were performed with PCR only when hepatitis occurred. RESULTS:At presentation 22 patients (22.4%) were positive for HBsAg, and 11 (15.9%) were positive for anti-HCV. Acute hepatitis developed in 12 (12.2%) NHL patients: 8 (out of 22) in HBsAg-positive and anti-HCV-negative patients, 3 (out of 76) in HBsAg-negative patients, and 1 (out of 11) in anti-HCV-positive patients. Hepatitis was attributed to reactivation of chronic B hepatitis in 3 patients and to drug toxicity in 3 others; hepatitis was undefined in 6 cases. INTERPRETATION AND CONCLUSIONS:Drug-related liver toxicity is not a rare occurrence in NHL patients. Reactivation of HBV replication is responsible for a relevant number of the hepatitis cases observed. We did not detect acute hepatitis due to the reactivation of HCV replication (in chronic C hepatitis carriers).

PATIENTS AND METHODS:Ninety-five patients with previously untreated, advanced or unfavorably presenting Hodgkin's disease were recruited in ten centers. Twenty-five patients with stage II-A-bulky disease received four courses of EBVD (epirubicin, bleomycin, vinblastine, dacarbazine) plus involved field radiotherapy (Group 1); 24 patients in stage I-B, II-B and III-A received 6 courses of EBVD (11 of them also received radiotherapy on bulky localizations (Group 2); 46 patients in stage III-AS > or = 3 nodes, III-B and IV received MOPP/EBVD 4 + 4 courses (Group 3). RESULTS:Eighty patients (84%) achieved CR, eight patients (8%) a PR, five patients did not respond and two progressed during therapy. CRs were achieved by 23/25 patients (92%) in Group 1, 21/24 (87%) in Group 2 and 36/46 (78%) in Group 3. The mean duration of follow-up was 33.3 months (range 5-69). There were three deaths from directly treatment-related causes. Twelve patients suffered chronic toxicity, including six who suffered lung toxicity and two who developed secondary myelodysplasia. CONCLUSIONS:The results achieved in this co-operative study are similar to those reported by most single-Institution trials and those with adriamycin-containing regimens. Long-term toxicity deserves careful consideration.

This study reports a case of granulocytic sarcoma that developed in the epidural zone 25 days before clinical evidence of an acute promyelocytic leukemia. The case presented the diagnostic difficulties that are common to all aleukemic granulocytic sarcomas. Moreover, it highlights the very rare association between granulocytic sarcoma and acute promyelocytic leukemia, which is far from being explained.

AIM:The occurrence of unilateral involvement in bilateral bone marrow trephine biopsies in non-Hodgkin's lymphomas (NHL) at disease onset (10-20% of cases) has been reported since the early 70s. Therefore, although these studies were based on small series, the use of bilateral bone marrow biopsies has become the rule. However, the clinical value of this procedure has never been clearly established. The aim of the present study was to ascertain the true value of bilateral bone marrow biopsy in the staging of NHL.STUDY DESIGN:We examined 368 cases of NHL (A-H according to the Working Formulation) (WF), without leukemic involvement of the peripheral blood, in order to evaluate: 1) the incidence of unilateral bone marrow involvement; 2) the percentage of patients who, as a result of unilateral bone marrow involvement, changed from stages I-II to stage IV; 3) assessment of response to therapy for patients with both bilateral or unilateral bone marrow involvement.RESULTS:In the A-C NHL groups of WF there was a unilateral bone marrow involvement of 8.8%. Overall, bone marrow involvement induced a change from clinical stages I-II to stage IV in 5.6% of cases, a figure which would correspond to a false negative rate of 2.8%, if unilateral bone marrow biopsy was performed. In the D-F and G, H groups of WF, unilateral involvement was 10.1% and 8.5% respectively; the change in stage from I-II to IV by unilateral bone marrow involvement respectively amounted to 1.4% and 2.8%, which correspond to respective false negative rates of 0.7% and 1.4%.CONCLUSIONS:On the basis of these results and of the present therapeutic strategies, we propose: bilateral bone marrow biopsy for clinical stages I-II of all NHL; no bone marrow biopsy at disease onset for clinical stages III and IV of A to H histologic subtypes of the WF; unilateral bone marrow biopsy (A-C subtypes of the WF) or bilateral (D-H of the WF), after the regression of extramedullary localizations.

We report the case of an elderly woman with polycythemia vera submitted to bone marrow biopsy who developed retroperitoneal hemorrhage as a result of direct penetration of the needle through the iliac crest, with damage to the iliolumbar artery, the first branch of the hypogastric artery.

Prolymphocytic leukemia (PLL) is a malignant lymphoproliferative disorder, characterized by massive splenomegaly, predominance of prolymphocytes in the peripheral blood and bone marrow, minimal lymph nodes enlargement and poor prognosis. It accounts for a 5-10% case of chronic lymphocytic leukemia (CLL). Patients age is usually over the fifth decade, the disease is 4.1 more common in males. More than 80% are B-lymphocytic derived cells showing a post-thymic phenotype. Median survival of B-PLL patients is 3 years, while only 7 months in T-PLL. Standard therapy of CLL with alkylating agents and prednisone have been not much effective in the treatment of PLL with a response rate of about 20%. Up to date no ideal treatment is available for PLL. A realistic goal is probably to achieve a clinical course transformation, from aggressive to mild, thus changing from short to long term prognosis. For this purpose the initial therapeutic approach cannot be limited to a single agent only. Splenic irradiation, intensive anthracyclines-based regimens, leukapheresis combine together represent the best therapeutic choice. Alkylating agents with or without prednisone may play a role in keeping indolent clinical course. Fludarabine has shown antileukemic activity against PPL even in patients resistant.

We report a case of idiopathic hypereosinophilia syndrome (H.E.S.) with a pronounced myeloproliferative disorder, which during the course of the illness has exceeded more than one "blastic crisis". This again proposes the difficult relationship between H.E.S. and myeloproliferative syndromes (M.S.), and is indicative of why some cases of H.E.S. are differentially diagnosed as chronic myeloid leukemia (C.M.L.) with an eosinophilic component.

We have analyzed 263 consecutive patients with chronic-lymphocytic leukemia. They all have been studied according to five different staging systems respectively proposed by Rai (1975), Binet (1977), Binet again (1981), Baccarini (1982) and Rozman (1984). All these procedures proved to be effective, because they divided our cases in groups with significant differences in survival time. The paper displays features and usefulness of each staging system.

introduction of 100 U/ml insulin is difficulty in measuring small doses, but this does not seem to be a problem with modern disposable syringes, even though it might be with the current British Standard glass syringe. Twenty (51),,) patients had previously used the 20 mark/ml scale and preferred the new scale with direct-reading 80 marks or units/ml; 28 (72°,,) thought that errors of doses were less likely with the syringes with the new scale; 35 (90",,) preferred the disposable syringes to the glass syringes, while two found them equally convenient and two found them inferior. Twenty-six (67,,)) said they would be willing to pay 5p per syringe for the convenience of using it, whereas only 23)''. said they would be willing to pay 10p per syringe. This study supports the advantage of changing to disposable syringes. A surprising number of patients would appear to be willing to purchase a well-designed disposable syringe-needle combination in preference to current glass syringes. With regard to multiple use of disposable syringes, crystalline insulins occasionally block the needle and prevent reuse. Several of our patients have commented that the needles become considerably less sharp after three or four uses. Even with that amount of reuse, it would probably be advantageous for the DHSS to supply disposable syringes rather than the current glass syringes, particularly if one takes into account the cost of insulin discarded on washing the glass syringes. M R PHILLIPS S STRANG G WERTHER D BAUM R C TURNER

Personal experience in the management of three cases of primary hyperaldosteronism, in which a cure was obtained by surgical removal of an adrenocortical adenoma, is was used in the elaboration of a diagnostic procedure requiring hospitalisation for 12 days. During 6 days, the patient is kept on a diet containing 100 mEq Na and K, and blood potassium values are repeatedly determined. Other causes of hypertension are ruled out. On the 6th day, baselines for blood renin and urinary aldosterone are calculated. Next, a hyposodic diet is given for 4 days, and a diuretic is administered on the last of these days, after which renin is determined "in response to stimulation". Lastly, two days of i.v. NaCl loading are followed by the determination of urinary aldosterone "during inhibition". If the picture is positive for hyperaldosteronism, the patient is discharged and followed during treatment with spironolactone, and eventually subjected to renal and adrenal arteriography to determine the site of the adenoma. Division of the procedure into increasingly complex steps enables the examination to be halted at any point when evidence in support of the suspected diagnosis fails to appear. This feature, coupled with the simplicity of the procedures adopted, enables all young subjects admitted for unexplained hypertension to be screened for hyperaldosteronism, with the assurance of obtaining certain diagnosis without an excessively long stay in hospital.