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In January 1987 we started a multicenter study in order to evaluate in adult ALL patients the results of an intensive chemotherapy effected early after CR, and to compare the efficacy of allogeneic BMT vs autologous BMT vs prolonged intensive chemotherapy in the attempt to eradicate minimal residual leukemia. To September 1990 ninety-six patients entered this study; of the 87 evaluable for induction 25 were at low risk and 62 at high risk; 67 (77%) achieved CR by an induction chemotherapy including vincristine, adriamycin, cyclophosphamide, dexamethasone. Fifty-six out of 67 remitters were enrolled for the early intensification, which consisted of HDAra-C+amsacrine (or IDAra-C+mitoxantrone) followed by vincristine+adriamycin+cyclophosphamide and etoposide+Ara-C. During the early intensification an unexpectedly high number of relapses (10/56) was observed, showing that very intensive treatment with myelosuppressive agents is not useful at this point of the post-remission therapy. One patient suffered toxic death. Out of 45 patients who completed the early intensification 16 had a related well-matched donor and were selected for allogeneic BMT (performed in 11); of the remaining 29 patients, 14 were randomized for autologous BMT (performed in 9) and 15 for a second intensification. The overall DFS at 3 years is 35%. The high number of early relapses makes it difficult to draw conclusions from the comparison of the three eradication modalities. The best results, although without statistical significance, were obtained after allogeneic BMT; in high-risk patients this procedure should be effected as soon as possible after attainment of CR. Autologous BMT and prolonged intensive chemotherapy gave results similar to each other; both were sometimes followed by delayed relapses.

In the chicken, three tenascin variants have been characterized that are generated by alternative splicing of 3 of its 11 fibronectin type III repeats. Using monoclonal antibodies that react with common regions versus extra repeats of tenascin, we could distinguish and separate tenascin variants and investigate their interaction with fibronectin using multiple experimental procedures. Interestingly, in all assays used the smallest tenascin variant bound more strongly to fibronectin than the larger ones. These biochemical data were paralleled by the observation that in chick embryo fibroblast cultures only the smallest form of tenascin could be detected in the fibronectin-rich extracellular matrix network laid down by the cells. Furthermore, each tissue present in adult chicken gizzard contained a distinct set of tenascin variants. Those tissues particularly rich in extracellular matrix, such as the tendon, contained the smallest tenascin only. Intermediate-sized tenascin was present in smooth muscle, whereas the largest form was exclusively detectable underneath the epithelial lining of the villi. Thus it appears that cell type-specific forms of tenascin exist that are appropriate for the functional requirements of the respective extracellular matrices.

Background: Treatment of older patients with non-Hodgkin's lymphoma (NHL) is difficult and conflicting. Lower responsiveness to therapy has been reported; however, the high risk of treatment morbidity, drug-dose reduction, and the occurrence of unrelated deaths might account for the poor outcome of NHL in the elderly., Methods: We retrospectively analyzed the therapeutic approach and the outcome in 90 NHL patients aged 65 years or older. Histologic classification was according to the Working Formulation., Results: Twenty-nine patients with low-grade NHL have been managed conventionally: complete response (CR) rate was 34.5% and median overall survival was 35 months. Sixty-one patients with intermediate-grade (IG, 36 cases) or high-grade (HG, 25 cases) NHL were treated as follows: 5 stage I-IE cases underwent radiation therapy; of 56 stage II-IV patients, 14 had conservative single-agent therapy and 32 received an attenuated CVP regimen. Only 10 patients were considered suitable for attenuated CHOP or CHOP-like programs. Overall CR rate was 50% for IG and 32% for HG NHL: Median survival was 33 months and 10 months (p less than or equal to 0.05), respectively. For IG and HG patients, the attainment of CR influenced survival significantly. Treatment morbidity was observed in 41% of patients. Resistant lymphoma was the major cause of death (31/36) during the first six months of therapy., Conclusions: In our experience, the outcome of elderly NHL patients treated with conservative therapeutic approaches is poor. Intensive chemotherapy regimens tailored to individual patients are needed to improve clinical results.

A study of the predictive value for CR, DFS and OS of the presenting features was carried out on 180 patients with advanced stage DLCL treated with MACOP-B between June 1986 and March 1989. A multivariate regression analysis identified LDH level, bone marrow involvement and tumor burden as independent risk factors with a 4 year survival rate of 79%, 58% and 28% respectively. Therefore MACOP-B proved to be an adequate treatment for the first two groups of patients but not for the third which requires a more aggressive treatment. A sequential single drug high dose chemotherapy with collection of peripheral blood stem cell program followed by bone marrow harvesting, super-intensive radio-chemotherapy and bone marrow transplant has been activated. Seven patients have been so far enrolled: preliminary results demonstrated the feasibility of the program. A larger number of cases and a longer follow-up is required for assessing the efficacy of this approach.

Fifty cases of Hodgkin's disease in intravenous drug users (IVDU) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (G.I.C.A.T.). Ninety-two per cent of the patients were males; the median age was 26 years. Persistent generalized lymphadenopathy (PGL) at onset was present in 54% of patients, AIDS in 9%, ARC in 9% while 28% were simply HIV-positive. The initial median absolute number of CD4 lymphocytes was 264/mmc. Opportunistic infections were diagnosed in 20% of patients. In most patients the histological pattern was that of mixed cellularity and lymphocytic depletion (76%). In almost half the initial symptom was a persistent lymph node enlargement due to PGL. In the majority of patients (58%) only a clinical staging and bone marrow biopsy could be performed due to the presence of opportunistic infections, rapid disease progression or refusal of pathologic staging procedures. One patient presented with a Waldeyer's ring involvement, but no other unusual presentations were observed. After MOPP alternated or followed by ABVD or MOPP alone, 15/29 CR (52%) and 14/29 PR (48%) were observed. The median duration of CR was 14 months, while the median survival of CR has not been reached; the median survival of patients treated with chemotherapy with CD4 values at presentation {geq}400/mmc was significantly superior to that in those with CD4 < 400/mmc. The overall median survival was 16 months. Twenty-eight per cent of patients receiving chemotherapy + radiotherapy developed opportunistic as well as non-opportunistic infections (21%). Lethal hepatic toxicity was observed in 2 patients. In conclusion, Hodgkin's disease in IVDU was not found to be associated with unusual presentations, as previously reported for homosexuals. Complete remissions could be achieved in over 50% of patients, but in IVDU non-opportunistic infections in addition to opportunistic infections may also limit treatment administration. The presence of parenchymal functional impairment due to drug abuse, or drug abuse-related infections, such as pneumonia, endocarditis and hepatitis, should lead to the choice of antitumour agents with no or only minor potential liver, lung and cardiac toxicity.

We have retrospectively analyzed the characteristics of 24 adult patients affected with non-endemic Burkitt's lymphoma (BL) and Burkitt cell acute leukemia (L3 ALL). The median age of the entire group was 29 years with a male preponderance (75%). Median LDH value was 580 mU/mL. Test for HIV-antibodies was carried-out in 16 patients; 5 of them (21%) showed HIV positive. CNS was involved in 25% of patients at diagnosis. In all cases studied for karyotype, the t(8;14) translocation was evident. As to therapy, 5 patients were not evaluable for early death, 12 were given an intensive ALL program, 5 a cyclic chemotherapy and 2 a new protocol alternating high-dose cyclophosphamide, high-dose cytarabine with mitoxantrone and the CHOP regimen. The overall complete remission rate was 42%; among 7 remitters, 4 have relapsed so far within a median time of 6 months. Three of 13 (23%) patients with lymphoma presentation are long remitters and may be cured; all cases had stage II disease and low LDH at diagnosis (less than 250 mU/mL). No patients with Burkitt's leukemia survive. CNS disease (8 cases) and septic shock (6 cases) were the most frequent terminal events. In our experience, the prognosis of advanced stage BL and L3 ALL in adults does remain dismal; the high prevalence of CNS disease and HIV-positivity may have contributed to the poor outcome.

A computer simulation (KINSIM) modeling up to 33 competing reactions was used in order to investigate the product distribution in a template-directed oligonucleotide synthesis as a function of time and concentration of the reactants. The study is focused on the poly(C)-directed elongation reaction of an oligoguanylate (a 7-mer is chosen) with guanosine 5'-monophosphate-2-methyl-imidazolide (2-MeImpG), the activated monomer. It is known that the elongation of oligoguanylates to form oligomeric products such as 8-mer, 9-mer, 10-mer, etc., is in competition with (1) the dimerization and further oligomerization reaction of 2-MeImpG that leads to the formation of dimers and short oligomers, and (2) the hydrolysis of 2-MeImpG that forms inactive guanosine 5'-monophosphate, 5'-GMP. Experimentally determined rate constants for the above three processes at 37 degrees C and pH 7.95 were used in the simulation; the initial concentrations of 2-MeImpG, [M]o, and of the oligoguanylate primer, [7-mer]o, were varied, and KINSIM calculated the distribution of products as a function of time until equilibration was reached, i.e., when all the activated monomer has been consumed. In order to sort out how strongly the elongation reaction may be affected by the competing hydrolysis and dimerization, we also simulated the idealized situation in which these competing reactions do not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Seventy-seven patients with relapsed or refractory acute leukemia and three with acute blastic chronic myeloid leukemia (CML) were treated in an open Phase II study using mitoxantrone 12 mg/m2 intravenously daily X 5 days. Complete remission (CR) was achieved in 32 of 80 (40%), including 23/45 (52%) with relapsed acute nonlymmphocytic leukemia (ANLL), four of 12 (33%) with relapsed acute lymphocytic leukemia ALL, four of 17 (24%) with ANLL refractory to daunorubicin + cytosine arabinoside, and one of three (33%) with refractory ALL. None of the patients with acute blastic CML achieved CR. Median survival time for all patients was 121 days. Median duration of complete response was 303 days with ten of 32 patients in continuing CR for periods varying from 44+ to 1210+ days. Apart from moderately prolonged hematologic suppression toxicity was mild and subjective side effects were tolerable. Mitoxantrone is an active agent in the treatment of acute leukemia and demonstrates incomplete cross resistance with duanorubicin. Mitoxantrone should be considered for first-line therapy in ANLL.

Twenty-five adult patients with resistant or early relapsing Hodgkin's disease have been treated with CAV combination chemotherapy (CCNU, melphalan and etoposide). All patients had previously received both MOPP and ABVD regimens (23 patients as primary therapy and two as first salvage). High-energy radiotherapy had been administered in one case. The CAV chemotherapy was used as first salvage therapy in 15 cases (60%); the remaining patients had been heavily pretreated with different regimens including alkylating agents, vinblastine, and/or nitrosourea derivatives before CAV for multiple relapses or progressive disease. At the initiation of CAV chemotherapy, 64% of patients had extranodal disease (20% with more than one site), and bone marrow was involved in 16% of total cases. Thirty-two percent of CAV patients had progressed during primary therapy, while only 20% of cases had relapsed after complete remission (CR). The CR rate after CAV therapy was 17% (4 of 24); partial responses were observed in 33% of patients, giving an overall response rate of 50%. The response was influenced by the presence of nodal disease and by a prior response to chemotherapy. Considering the 15 patients who received CAV therapy as first salvage, the CR rate was 37%. The median survival from the initiation of CAV therapy was 23 months for the whole group of patients, and was not reached at 2 years for those who received CAV as first salvage therapy. Toxicity consisted of nausea (100% of cases), vomiting (63%), reversible alopecia (83%), mild to moderate leukopenia and thrombocytopenia (54% and 21%, respectively). No therapy-related deaths were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

The chest radiograms (CXR) of 102 patients with Hodgkin's disease presenting with mediastinal involvement at diagnosis were reviewed to assess the incidence and relevance of residual mediastinal abnormalities after therapy. All patients had completed planned treatment and had no evidence of persisting extramediastinum disease at restaging. Thirty-nine cases (38 per cent) showed residual mediastinal widening at the end of therapy (minimal changes in nine and measurable changes in 30 cases). Neither presenting features nor treatment modality correlated with residual mediastinal mass on chest X-ray. The isolated intrathoracic relapse rate was 11 per cent for patients with normal mediastinum following therapy, as compared with 20.5 per cent for those with residual widening; this difference did not reach statistical significance (p = 0.3). The persistence of mediastinal abnormalities was associated with a trend towards a higher risk of intrathoracic relapse for patients with initial bulky disease (p less than 0.05) and for those with B symptoms (p = 0.07). Using thoracic CT scan for restaging (56 patients), the residual mediastinum rate rose to 70 per cent; the predictability of local relapse with this procedure was not greater than with conventional X-ray study.

Norfloxacin (NOR) or cotrimoxazole (TMP/SMX) were randomly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections. Nineteen NOR patients (65%) and 22 TMP/SMX patients (73%) complained of febrile or infectious episodes during the study. The mean incidence of febrile complications per patient was higher in the TMP/SMX group: 1.05 vs 0.68 (p less than 0.05). Eleven of 16 microbiologically documented infections in the TMP/SMX group and 7 of 11 in the NOR group were caused by gram negative bacilli (GNB). NOR recipients had fewer days of fever, fewer days on parenteral antibiotics and a lower proportion of time spent febrile. Fecal surveillance cultures showed intestinal GNB colonization in 42/80 specimens in the TMP/SMX group (resistant strains: 93%) and in 8/75 specimens in the NOR group (1 resistant strain). Overall, NOR seems to be effective in eradicating GNB from the digestive tract without selection of resistant strains and in preventing febrile episodes in neutropenic patients.

Because of the reported high sensitivity of acute promyelocytic leukemia to daunorubicin, we treated 27 consecutive, newly diagnosed, acute promyelocytic leukemia (APL) patients with the new anthracycline idarubicin (IDA) as induction therapy. IDA dosage ranged from 0.25 to 0.30 mg/kg/day and the drug was administered as single agent during a single induction course of 6 days. A total of 22/27 patients (81%) achieved complete remission, 4 (15%) died during induction and 1 patient was resistant to IDA. Extrahematological toxicity was acceptable. A total of 13/22 patients having achieved CR are still alive and in first CR after a median follow-up of 12 months. As for the treatment of the coagulopathy present in APL: 17/27 (63%) received tranexamic acid (6 g/daily) in continuous infusion for total of 7 d. None of the patients treated with tranexamic acid experienced thromboembolic complications. In conclusion, this multicentric pilot study confirms the antileukemic potency of IDA and the high sensitivity of APL to anthracycline derivatives.

Of 349 consecutive patients with Philadelphia-positive chronic myelogenous leukemia (Ph' + CML), 14 (4%) developed extramedullary disease (EMD) during their illness. The sites of EMD were: bone (57%), lymph nodes (29%), skin and soft tissues (21%), central nervous system (14%). The median time from diagnosis of CML to the occurrence of EMD was 48 months. At the time of diagnosis of EMD, 7 patients were hematologically in chronic phase, while 7 showed features of accelerated or blastic CML. For patients lacking medullary blastic transformation criteria, the median time from diagnosis of EMD to blast crisis was 4 months. The overall median survival from development of EMD was 5 months. In conclusion, EMD may occur during the course of CML either in the context of a frank blastic transformation, or as an isolated tumoral infiltrate which heralds an impending blast crisis. Its recognition requires a prompt change to acute-phase chemotherapy.

The Italian Cooperative Group on AIDS-related tumors has collected 435 cases of HIV-associated tumors since December 1986. The following conclusions can be drawn from this IVDA-based series: (1) at least 15% of AIDS cases are associated with tumors; (2) the number of malignant lymphomas (high-grade non-Hodgkin's lymphoma [NHL], Hodgkin's disease [HD] is comparable to that of Kaposi's sarcoma (KS) (188 vs. 198); (3) KS among AIDS patients is less common than in countries where homosexual men are the main group affected by AIDS. However, KS also affects intravenous drug abusers (IVDA) almost exclusively males, with characteristics similar to those observed among homosexual men; (4) HD is associated with an aggressive course; (5) anal and oral primary tumors as well as oral and anal involvement of NHL are very rare; (6) testicular cancers occur in patients mainly with early HIV infection, without adversely affecting the dosage of radiotherapy and chemotherapy; (7) cervical cancer successfully treated with conization suggests that PAP test screening in young IVDA women is warranted; (8) lung cancer occurs in a young age group with rapid progression and death.

Since December 1987, 115 patients with HCL have been enrolled in a prospective multicenter study to evaluate the role of splenectomy after an induction therapy with alpha interferon. The group of patients was divided into two categories: those younger and those older than 65 years. The schedule of treatment with IFN was, respectively, 1.8 MU/sm/daily and 1.0 MU/daily, 33 patients were treated with r-alpha-2a, 34 with r-alpha-2b, and 25 with alpha-Ly. To date, 92 patients are fully evaluable. The response was assessed every 3 months by bone marrow trephine biopsy. Patients in CR continued IFN therapy for 3 months and, if they were still in CR, could undergo an optional splenectomy. Patients in PR continued therapy for 12 months and subsequently were randomized for splenectomy or observation only. In these preliminary results of an ongoing protocol, CR was obtained in 5 cases (6%), PR in 59 (64%), MR in 25 (27%), NR in 3 (3%). Only 2 of the 5 patients in CR underwent splenectomy and are still in CR. Of the 59 patients in PR, only 15 completed 12 months of therapy. 9 patients in Group A were randomized, 4 were splenectomized and 5 were in the observation arm. All patients were splenectomized safely and no complications occurred. These preliminary results suggest that splenectomy could be effective in consolidating the response obtained with IFN.

We report a case of acute promyelocytic leukemia who suffered spontaneous splenic rupture with massive hemoperitoneum while receiving intensive induction chemotherapy. Emergency computed tomography of the abdomen helped in the diagnosis of intra-abdominal bleeding. The patient was successfully treated with immediate splenectomy and made an uneventful postoperative recovery. Ten days after surgery chemotherapy could be resumed and complete remission was achieved. Although spontaneous splenic rupture is a rare complication of hematologic malignancies, this diagnosis should be considered in all patients with leukemia who develop acute abdominal pain with hypotension, even in the absence of splenomegaly.

Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long-term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha-interferon (IFN) exerts a dose-dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non-mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha-IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1-3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9-12 months). Also patients resistant to cytotoxic drugs may respond to alpha-IFN, suggesting a lack of cross-resistance between the two treatment modalities. Side-effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low-dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha-IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.

Treatment and outcome of 103 consecutive patients aged greater than or equal to 60 with de novo acute nonlymphocytic leukemia (ANLL) were reviewed. Twenty-three cases (22%) were not suitable for induction chemotherapy because of very poor presenting general conditions and could receive supportive care alone. The majority of them died within 1 month. Twenty-eight patients (27%) aged greater than or equal to 70 and/or with concurrent nonhematologic disorders underwent mild induction chemotherapy, which produced 3 complete remissions. The median survival for this group was 2 months. Only 52 patients (50%) were considered eligible for conventional induction chemotherapy. For this group, response rate was 34.5%, the median survival was 3.5 months, and median survival for responding patients was 13 months. Only intensive chemotherapy seems capable of substantially improving prognosis for older ANLL patients. This approach, however, is feasible only in a minority of patients, due to a high incidence of life-threatening complications.

Monosomy 7 is frequent in acute myeloid leukaemia (AML) and in preleukaemic dysmyelopoietic syndromes but often it is not the only chromosome anomaly associated with these conditions. We report 14 patients with "pure" monosomy 7 and their clinical and haematological data are analysed in order to clarify the possible implications of this chromosome anomaly. The following points are considered: 1) In spite of the apparent variability of clinical forms in which monosomy 7 is found, several characteristics are common to all monosomy 7 patients, i.e. the presence of a preleukaemic phase and blood and marrow features suggesting the early involvement in the disease of all marrow cell lines. The different diagnoses associated with monosomy 7 are correlated with different steps of a unique myeloproliferative disease whose typical course can be reconstructed. 2) Monosomy 7 has a negative prognostic value. When it is found in a preleukaemic disorder it indicates a high risk of progression to AML, while in AML it implies recurrent infections, poor response to therapy and short survival. 3) The significance of the lack of Colton blood group antigens in monosomy 7 patients is discussed, with particular regard to the fact that the patients in whom this lack was found are the only ones who had not received transfusions in the months before the tests were done. 4) The finding of defective neutrophil chemotaxis in monosomy 7 patients is confirmed and the clinical importance of this fact is emphasized. 5) The data on the 14 patients support the opinion that AML, in general, is heterogeneous in origin. It is postulated that monosomy 7 is a marker of a specific pathogenetic pathway of AML, which implies the beginning of the malignancy in a pluripotent stem cell.

We have analyzed the distribution of terminal deoxynucleotidyl transferase (TdT) in 30 patients with myelodysplastic syndromes (MDS), in connection with morphology, cytochemistry, and cytogenetics. All cases in preleukemic phase were strictly TdT-negative. At variance, 4 (19%) of 21 cases with subsequent leukemia were TdT-positive and showed a pure lymphoid (one case) or a mixed lymphoid-myelomonocytic (three cases) morphology. The TdT enzymatic activity ranged from 2 to 21 U/10(8) cells and the percent of positive cells in the immunofluorescence test ranged from 10 to 80% of total. All cases were Philadelphia chromosome-negative. The clonal origin of MDS from the pluripotent stem cell, capable of originating both a lymphoid and myeloid progeny, is further corroborated.

We have analyzed the distribution and prognostic significance of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) in connection with conventional cytology, cytogenetics, response to therapy, and survival. The study population consisted of 78 patients with AML, 44 patients with Ph1 + CML in chronic phase, and 35 adult patients with Ph1 + CML in blastic phase, among which 5 cases presented as Ph1 + acute leukemia. Nine percent of the AML cases were positive for TdT and were characterized by a high percentage of blast cells in bone marrow, myeloid features by cytochemistry and absence of the Philadelphia chromosome. The median ADA values of the TdT+ AML cases were several times higher than those obtained for the TdT- cases. The survival calculated for the two groups of AML cases subdivided according to ADA levels was significantly longer (p less than 0.025) for the patients with low levels of ADA (less than 250 U/10(8) cells). In chronic phase of CML, TdT was absent and ADA values were increased over normal controls only in cases with early signs of transformation. In blastic phase, 31% of the 35 cases were positive for TdT, and ADA values were significantly higher (p less than 0.001) in TdT+ than TdT- cases. The survival calculated from the onset of transformation was significantly longer for the TdT+ acute phase (10.4 mo) compared to the TdT- patients (4.8 mo; p less than 0.025). Four cases presenting as Ph1 + acute leukemia were TdT+ and had elevated levels of ADA; 3 of them responded to ALL therapy, reverting to a stable phase of CML.

Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.

Magnesium, an ion necessary in enzymatic as well as in nonenzymatic template-directed polynucleotide-synthesizing reactions, has been found to catalyze the hydroxide ion attack on the P-N bond of selected 5'-monophosphate imidazolide derivatives of nucleotides, such as guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG), guanosine 5'-monophosphate imidazolide (ImpG), and adenosine 5-monophosphate 2-methylimidazolide (2-MeImpA). Calcium ion behaves similarly, but quantitatively the effects are smaller. Pseudo-first-order rate constants of 2-MeImpG and ImpG hydrolysis as a function of Mg2+ concentration have been obtained in the range 6 < or = pH < or = 10 at 37 degrees C. Mg2+ catalysis is particularly effective around pH 10 where a 0.02 M concentration leads to 15-fold acceleration and a 0.2 M concentration to a 115-fold acceleration of the rate. At other pH values Mg2+ catalysis is less dramatic, mainly because the noncatalyzed reaction is faster. Mg2+ catalysis is attributed to the reaction of the zwitterionic form of the substrate (SH+/-, imidazolide moiety protonated) with OH- rather than reaction of the anionic form (S-, imidazolide moiety deprotonated) with water. This conclusion is based on a study of the N-methylated substrates N-MeImpG and 1,2-diMeImpg, respectively, which were generated in situ by the equilibrium reaction of ImpG with N-methylimidazole and 2-MeImpG with 1,2-dimethylimidazole, respectively. In contrast, the absence of Mg2+ the reaction of S- with water competes with the reaction of SH+/- with OH-. The present study bears on the mechanism of the Mg2(+)-catalyzed template-directed synthesis of oligo-and polynucleotides derived from 2-MeImpG and on the competition between oligonucleotide synthesis and hydrolysis of 2-MeImpG.

This paper reviews the major information on lymphoproliferative diseases developing in primary and acquired immunodeficiencies, in organ allograft recipients, and in different diseases with immune impairment such as rheumatoid arthritis, angioimmunoblastic lymphadenopathy, and Hodgkin's disease (secondary lymphomas). The hypothetical role of Epstein-Barr virus (EBV) in the pathogenesis of lymphoproliferative diseases in immunocompromised hosts has come from the examination of lymphoma cells or tissues for Epstein-Barr nuclear antigen (EBNA), or carriage of the viral genome, and will be extensively reviewed. The characteristics and the prognosis of high-grade lymphomas developing in the acquired immunodeficiency disease (AIDS) will be analyzed, together with their pathogenetic mechanisms, with particular emphasis on the constant presence in the lymphoma cells (mostly of Burkitt-type) of the c-myc oncogene rearrangement and activation. The principal methods of study of secondary lymphomas and major attempts at therapy will reviewed as well.

481 cases of adult leukemia (115 acute lymphoblastic leukemia, ALL, and 366 acute nonlymphoid leukemia, ANLL) diagnosed at the Hematology Division of Pavia between 1976 and 1985 were reviewed to evaluate how many patients had an aplastic presentation. In 8 cases (1.6%) typical marrow hypoplasia preceded overt leukemia. At the leukemic transformation, the morphological and immunological findings were diagnostic for non-T non-B ALL in 2 cases, for ANLL in 5 cases (2 M1, 2 M2, 1 M5) and for Ph'-negative chronic granulocytic leukemia in 1 case. Median survival from the onset of leukemia was 5 months. In a certain proportion of cases aplastic anemia may be considered as a preleukemic state with a low propensity to develop into acute leukemia.

The in vitro effects of a pentoxifylline solution on hemoglobin-oxygen affinity and electrolytic distribution between plasma and red blood cells were evaluated. Pentoxifylline increased intracellular pH and decreased extracellular pH. There were no exchanges of Na+, K+, Ca++ and Cl- between plasma and red blood cells. Red blood cell content of 2,3-diphosphoglycerate remained unchanged, while P50 was reduced as a consequence of the intracellular alkalosis. The possible implications of the metabolic effects of pentoxifylline on red blood cell deformability and 2,3-diphosphoglycerate content in vivo are discussed.

Fifty untreated adult patients with advanced Hodgkin's disease (HD) were given alternating MOPP-ABVD chemotherapy in a prospective eight-cycle program. This series included 33 patients with stage II-III disease and bulky lymphoma and/or B symptoms, and 17 patients with stage IV disease. Nodular sclerosis amounted to 52%, and systemic symptoms were present in 70% of patients. The median follow-up was 50 months from the initiation of therapy (range: 36-78 months). The complete remission rate was 80%, with no differences according to the main patient characteristics before therapy, except for bulky (65%) versus non bulky (88%) disease (p = 0.05). The actuarial 4-year overall (OS) and relapse-free survival were 78% and 71%, respectively. No clear-cut pretreatment characteristics showed an influence on survival, although there was a trend favoring non bulky versus bulky disease (p = 0.08). The actuarial 4-year OS of complete responders was 92%; all 13 patients who died had evidence of HD; the cause of death was disease progression and organ failure in 11 cases, acute myelomonocytic and opportunistic infections with AIDS in the other two cases, respectively. No severe pancytopenia episodes or life-threatening complications occurred during therapy; gastrointestinal and neurological toxicity were mild and no patient refused to complete the treatment. Menstruating women were given estrogen-progesterone combinations, and all continued to have regular menses throughout chemotherapy and afterwards; a young woman had a normal pregnancy resulting in a normal live birth. Only one case of stable amenorrhea was observed. Oligospermia after chemotherapy was seen in seven of 10 tested males, and azoospermia in one case.(ABSTRACT TRUNCATED AT 250 WORDS)