Validation of the international prognostic index in working formulation group A low-grade non-Hodgkin's lymphoma: retrospective analysis of 137 patients from the Gruppo Italiano per lo Studio dei Linfomi registry.

BACKGROUND AND OBJECTIVE: The subset of non-follicular non-Hodgkin's lymphoma (NHL) includes patients with varied prognoses, thus suitable for different therapeutic approaches. The International Prognostic Index (IPI), originally proposed for aggressive NHL, has been demonstrated to be of prognostic relevance also in follicular NHL. The main aim of the study was to validate the IPI in this histologic category; in addition, the specific prognostic classification, currently employed in the Gruppo Italiano per lo Studio dei Linfomi (GISL) prospective therapeutic trials and based on different features, more similar to those applied to chronic lymphocytic leukemia, was analyzed. DESIGN AND METHODS: The present series consists of 137 evaluable patients affected by Working Formulation group A NHL out of 256 cases referred to the GISL Registry. The retrospective prognostic study included the evaluation by both univariate and multivariate analyses of overall survival, response to therapy and response duration. The IPI was applied as originally proposed. The GISL definition of indolent and aggressive disease at diagnosis was based on the presence of B symptoms, bulky disease, anemia and thrombocytopenia. RESULTS: The distribution of patients in IPI risk groups was rather unbalanced with 18%, 47%, 28% and 7% of cases classified as low (L), intermediate-low (IL), intermediate-high (IH) and high (H) risk, respectively. The median overall survival was not reached in either L or IL risk groups, and was 84.1 and 7.4 months for IH and H risk groups, respectively (p=0. 0005). A simplified IPI model was designed merging patients in both intermediate risk groups and the statistical difference of survival retained its significance. GISL prognostic stratification was demonstrated to have a significant association with survival, with a median survival of 71.3 months in aggressive disease and a median survival not reached at 152 months in indolent disease. Both the simplified IPI model and the GISL risk definition retained their significance in multivariate analysis for overall survival, while for response to therapy only the simplified IPI model resulted to be of statistical significance. In addition, the GISL prognostic stratification identified patients with different outcomes within the IPI intermediate risk group, with a median survival of 70.2 months for patients with aggressive disease wheras the median survival for those with indolent disease was not reached. Finally, a prognostic score resulting from the integration of the simplified IPI and the GISL system was statistically validated. INTERPRETATION AND CONCLUSIONS: The retrospective analysis of this series demonstrates the validity of the IPI in non-follicular indolent NHL and the usefulness of integrating the IPI parameters with disease specific prognostic variables.

Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease.

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow-up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin's disease, is needed.

A pilot study on the use of the ProMACE-CytaBOM regimen as a first-line treatment of advanced follicular non-Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND: The role of intensive conventional dose chemotherapy in advanced low grade non-Hodgkin's lymphomas is a matter of debate. The Gruppo Italiano per lo Studio dei Linfomi conducted a study to evaluate the efficacy and toxicity of a third-generation polychemotherapeutic regimen, ProMACE-CytaBOM, as a first-line therapy in a selected group of patients with advanced follicular non-Hodgkin's lymphoma (Fo-NHL) who were younger than 60 years. METHODS: Thirty-nine patients were included in the study (14 males, 25 females; median age, 44 years; age range, 22-60 years). Their WF histotypes were B (9 patients), C (23 patients), and D (7 patients). All of the patients had disease in an advanced clinical stage (Stage III, 15 patients; Stage IV, 24 patients), and 9 patients had B symptoms. According to the age-adjusted International Prognostic Index (IPI), 20 patients exhibited low-intermediate risk, 14 high-intermediate risk, and 5 high risk. Three of the patients were not considered evaluable because they withdrew their consent after three (one patient) and four (two patients) cycles of therapy (one of these patients was in complete remission [CR], and two were in partial remission [PR]). Of the 36 evaluable patients, 4 received IF-RT after the 6 planned cycles of therapy. RESULTS: CR was achieved in 20 patients (55.5%) and PR in 14 (38.8%). One patient (2.7%) experienced disease progression during the treatment program. Eight of the 20 patients with CR (40%) relapsed. Eight patients (22.2%) died: 6 died of disease progression, 1 died of therapy consequences, and 1 died of an unrelated cause. With a median follow-up of 49 months (range, 28-79 months), the disease free survival rate was 60%. The overall survival rate was 80% after a median follow-up of 44 months (range, 3-79 months). The IPI stratification of patients showed a borderline statistical difference in terms of time to treatment failure and overall survival. The main hematologic toxicity was neutropenia (Grade 3 in approximately 10% of patients). One patient died of sepsis. Cotrimoxazole prophylaxis was always given. Cardiac toxicity (Grade 3) was observed in 1 patient at the end of the planned therapy. The average relative dose intensity of the drugs was 89% of the projected dose, without the regular use of growth factors. CONCLUSIONS: This study indicates that ProMACE-CytaBOM could be a suitable regimen for adult patients with advanced Fo-NHL, allowing a good CR rate and very good disease free survival rate. However, the occurrence of severe, albeit limited, adverse effects suggests that this regimen should first be used in controlled therapeutic protocols to verify its efficacy with respect to less intensive approaches.

Hodgkin's disease presenting below the diaphragm. The experience of the Gruppo Italiano Studio Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Infradiaphragmatic Hodgkin's disease is rare, making up 5-12% of cases in clinical stages I and II; consequently, several questions concerning prognosis and treatment strategy remain to be answered. The aim of this study was to analyze the clinical and prognostic characteristics and outcome of this condition. METHODS: A series of 282 patients with CS I-II Hodgkin's disease (HD) was investigated. In 31 patients the disease was confined below the diaphragm (BDHD), and in the remaining above the diaphragm (ADHD). The presenting features and outcomes were compared in the two groups. RESULTS: The BDHD group was older (p < 0.0002), had a higher frequency of males (p < 0.08) and a different histological subtype group distribution (p < 0.0001). Stage II BDHD patients had a worse overall survival rate (OS) than stage II ADHD patients (68.8% vs 86.6% at 8 years, p < 0.01) if age is not considered; patients with more than 40 years of age, in fact, had the same survival rates as those with ADHD. BDHD patients with intra-abdominal disease alone had worse prognostic factors and OS (p = 0.12) than patients with inguinal-femoral nodes. INTERPRETATION AND CONCLUSIONS: Although BDHD patients present distinct features, they have the same OS and relapse-free survival rate as age-adjusted ADHD patients. According to our experience patients with stage I peripheral BDHD respond well to radiotherapy-based regimens. Those with stage II and or intra-abdominal disease are more challenging; chemotherapy or a combined therapy seem to be more suitable approaches for these patients.

CCNU, vinblastine, procarbazine and prednisone (CVPP) with extended-field radiotherapy in the treatment of early unfavorable Hodgkin's disease. A prospective study on behalf of the Gruppo Italiano per lo Studio dei Linfomi (GISL).

PURPOSE: To test the adequacy of the CVPP four-drug regimen as ancillary chemotherapy associated with extended-field radiotherapy in the treatment of early, unfavorable, clinically staged Hodgkin's disease. PATIENTS AND METHODS: The population of this prospective, multicenter study consisted of 49 patients with stage I-II disease, associated with bulky involvement or unfavorable histology (lymphocyte-depleted nodular sclerosis or lymphocyte depletion), systemic symptoms or extranodal involvement, or presenting with stage III A favorable-histology disease, with or without extranodal involvement. RESULTS: Complete remission was achieved in 39 patients, partial remission in 2, while 8 patients did not respond. Four patients have relapsed so far (median follow-up: 43 months), all of whom were subsequently rescued with different salvage treatments. Dose intensity (mean +/- SD: 0.83 +/- 0.12) and hematological toxicity (including 2 deaths from infection) were higher when RT followed CT than when it was interposed in the middle of the 6 cycles. No growth factors were used. Nonhematological toxicity was very low and fully tolerable. CONCLUSIONS: Results confirmed the mild neurological and gastroenteric side effects of CVPP that make it an interesting MOPP-variant regimen. This combination seems most indicated when a regimen devoid of cardiac and pulmonary toxicity is required for association with full-dosage mediastinal radiotherapy, as is often the case in early, unfavorable Hodgkin's disease. The optimal sequence consists of radiotherapy administered after completion of the chemotherapy program. The use of growth factors for correction (or prevention) of marked leukopenia seems appropriate.

A prognostic index for multiple myeloma.

The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes (with median overall survival of 52, 28 and 13 months respectively) and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient.

Vinblastine, bleomycin, and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: the Gruppo Italiano per lo Studio dei Linfomi Experience.

PURPOSE: To ascertain whether vinblastine, bleomycin, and methotrexate (VBM) (CT) combined with extended-field radiotherapy (EF RT) is effective enough to spare laparotomy in early, favorably presenting Hodgkin's disease (HD) patients. PATIENTS AND METHODS: Fifty patients with clinical stage IA or IIA HD with favorable histology and no bulky masses entered a prospective multicenter study started in January 1988. The median follow-up time was 38 months. RESULTS: All patients achieved a complete remission (CR). Five relapsed after 3 to 40 months and underwent successful salvage therapy. The actuarial remission rate was 0.89% at 3 years and 0.82% at 5 years. Two patients died in CR: one of severe pulmonary toxicity, the other of a second neoplasia (adenocarcinoma of the lung), 2 and 43 months after the end of therapy, respectively. The hematologic toxicity recorded during VBM CT was mild on the whole. Major toxicity was represented by pulmonary side effects and neurologic symptoms. Multiple regression analysis demonstrated that pulmonary toxicity was significantly related only to the amount of RT delivered to the mediastinum and not to the relative dose of bleomycin, to the dose-intensities of the three drugs in the regimen, or to patient age or sex. The same statistical technique showed that the only clinical factor related to grade of neurotoxicity was vinblastine dosage. CONCLUSION: VBM CT combined with EF RT is an effective treatment for early, clinically staged, favorable HD patients. However, the toxicity of this combination suggests that certain modifications should be evaluated.

Anaplastic large cell lymphoma (CD30+/Ki-1+). Analysis of 35 cases followed at GISL centres.

Between January 1988 and June 1992, 35 patients with primary anaplastic large cell lymphoma (ALCL)CD30+ were referred to one of the institutions participating in GISL (Gruppo Italiano per lo Studio dei Linformi). 16 patients were treated with ProMACE-CytaBOM, two with MACOP-B, one with CHOP and one with LSA2-L2. As of November 1990, all newly diagnosed patients were treated with MOPP/EBV/CAD hybrid. 27 (77%) cases of ALCL CD30+ and 8 (23%) cases of Hodgkin's-related (HR) lymphoma CD30+ were diagnosed. Extranodal disease was present in 22 cases (63%), and 8 patients (23%) had primary bone marrow involvement. Twenty-three complete remissions (CR) (66%), six partial remissions (PR) (17%) and six no remissions (NR) (17%) were achieved with induction therapy. Results achieved with ProMACE-CytaBOM and MOPP/EBV/CAD hybrid were comparable. The overall response rate (CR+PR) was 85% for patients with classic ALCL CD30+ and 87% for those with HR lymphoma CD30+. The 3 year estimated overall survival rate was 66% and the 3 year relapse free survival rate was 65% for the entire group. The only significant favourable prognostic factor was the achievement of CR with initial therapy. Our findings suggest that ALCL (CD30+/Ki-1+) has a clinical outcome similar to aggressive non-Hodgkin's lymphoma (NHL). The use of an anthracycline-containing regimen will provide a change of cure in approximately 65% of cases.

ProMECE-CytaBOM vs MACOP-B in advanced aggressive non-Hodgkin's lymphoma: long term results of a multicenter study of the Italian Lymphoma Study Group (GISL).

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m2 of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure. Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Estimate of expected survival at diagnosis in Hodgkin's disease: a means of weighting prognostic factors and a tool for treatment choice and clinical research. A report from the International Database on Hodgkin's Disease (IDHD).

PURPOSE: The aim was to identify a mathematical model that, when fitted with the survival time distribution of a Hodgkin's disease population, would provide a reliable estimate of expected survival at diagnosis for any new Hodgkin patient. This model would be based upon a multivariable selection of the best prognostic factors evaluable at diagnosis and its forecast could be of assistance in the choice of treatment. METHODS: The study sample consisted of the 5,023 patients whose basic clinical information was collected into the IDHD. These were people treated with standard protocols over the last two decades in 18 institutions. Several survival time distributions (exponential, Weibull, Gompertz, log-logistic and log-normal) were investigated to find the one that best fit the data and to relate its parameters to patient prognostic characteristics. RESULTS: The log-normal model provided the best fit for the data. The most statistically significant prognostic covariates were stage, age, histotype, B symptoms, serum albumin, sex and involved area distribution. Mediastinal, extranodal or bone marrow involvement, erythrocyte sedimentation rate, hemoglobin, serum alkaline phosphatase and lactate dehydrogenase did not add significant information. An equation containing these seven variables was derived to estimate median survival. Five distinct prognostic classes were identified by four cut-off values for this estimate. CONCLUSIONS: Direct use of estimated median survival or allocating each patient into one of the five prognostic classes allows better tailoring of clinical strategies according to prognostic characteristics, more accurate patient stratification and evaluation of results in clinical trials and metaanalyses. Instructions are given for using this tool for both clinical and investigational purposes.

Primary splenic lymphoma: does it exist?

The number of primary splenic lymphomas being reported is increasing despite the rarity of this malignancy, but what really constitutes a lymphoma arising primarily in the spleen is still a matter of discussion. The authors choose the "restrictive" definition of a lymphoma involving the spleen and the splenic hilar lymph nodes only. In this way, the risk of epidemiologic or clinical overestimation is avoided. The clinical features of this condition are characterized by non specific symptoms and signs, while the prevailing histology is that of a low-grade or intermediate-type lymphoma. Disease spreading outside of the spleen and its hilar lymph nodes is the single most important factor associated with an unfavorable prognosis. From this usual clinical picture, two distinct nosologic entities can be outlined on the basis of histologic and immunologic peculiarities: splenic lymphoma with circulating villous lymphocytes and marginal-zone splenic lymphoma. The former arises from follicular center cells and is characterized by hypersplenism, variable percentages of circulating villous lymphocytes and, frequently, a monoclonal gammopathy. The latter originates from a peculiar splenic B-cell structure separated by the mantle zone. The proliferating cells are medium-sized KiB3-positive lymphocytes with round or cleaved nuclei and pale cytoplasm, which surround follicular centers and infiltrate the mantle zone. It is interesting that marginal-zone lymphoma cells share some of the characteristics of the lymphocytes involved in both lymphomas of mucosa-associated lymphoid tissue and the B-monocytoid lymphomas. Splenectomy is still the most effective therapy for all primary splenic lymphomas.

Study of prognosis in Waldenström's macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility.

Prognostic evaluation of Waldenström's macroglobulinemia (WM) is unreliable, few studies considered prognostic factors in WM and only one was derived from a multivariate analysis. One hundred forty-four retrospective, previously untreated patients with clinically overt WM were studied to learn whether overall survival was related to any of the various clinical features presented at diagnosis. Patients were homogeneously treated with intermittent doses of chlorambucil for as long as this showed an effect on the monoclonal component. The population was randomly subdivided into a 90-patient exploratory sample, on whom investigation would be conducted, and in a 54-patient test sample, on whom the results would be validated. In the exploratory sample univariate analysis identified the following parameters as the most important for prognosis: age (< or > or = 70 years), platelet count (< or > or = 120 x 10(9)/L), presence or absence of an abnormal number of red blood cells in the urine, hemoglobin concentration (< or > or = 9 g/dL), erythrocyte sedimentation rate (< or > or = 110 mm at first hour), presence or absence of cryoglobulinemia and of weight loss. Cox multivariate analysis showed that only hemoglobin, age, weight loss, and cryoglobulinemia independently affected survival. These four clinical variables were also shown to be able to discriminate survival significantly in the test sample. Moreover, it was possible to demonstrate (both in the exploratory and the test sample) that clear-cut, albeit dichotomic, survival discrimination can be reached with the presence at diagnosis of either no more than one, or any two or more, of these four prognosticators. These simple clinical criteria could be the basis of an initial binary, prognostic classification of WM, which could help in differentiating therapy according to the severity of the disease, and in properly designing future clinical trials.

MOPP/EBV/CAD hybrid chemotherapy with or without limited radiotherapy in advanced or unfavorably presenting Hodgkin's disease: a report from the Italian Lymphoma Study Group.

PURPOSE: We explored the feasibility, toxicity, and preliminary results of a chemotherapy (CT) regimen, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and vinblastine (EBV)/lomustine (CCNU), doxorubicin, and vindesine (CAD), derived through hybridization, shortening, and intensification of a corresponding 10-drug alternating combination CAD/MOPP/doxorubicin, bleomycin, and vinblastine (ABV), effective in treatment of advanced Hodgkin's disease (HD). PATIENTS AND METHODS: Hybridization involved all drugs except CCNU and mechlorethamine, which were administered in alternating cycles; the length of therapy was reduced from nine to six cycles. The average projected drug doses during the six cycles were increased by 42%, with an overall 1.54 dose-intensification; epidoxorubicin was substituted for doxorubicin at equivalent tumoricidal doses. Radiotherapy (RT) was optional and its indications were limited. RESULTS: Eighty assessable patients with previously untreated, advanced or unfavorably presenting HD were treated in nine cooperating institutions between 1988 and 1991. RT was delivered to 22 patients. Remissions were complete (CR) in 75 patients (93%), partial in three (4%), and null in two (3%). The median relative dose-intensity was 0.71 for the overall regimen. Three of five patients who failed to achieve CR, and two of the four who relapsed, received lower relative dose-intensive cycles. Nonhematologic toxicity was acceptable, but there was considerable hematologic toxicity. Fatal gastrointestinal bleeding was seen in one patient. CONCLUSION: Caution is advised due to the short median follow-up period. Nevertheless, in addition to the excellent response rate, (1) the results were reached through abbreviation, intensification, and hybridization of an existing alternating regimen; (2) RT had limited use in this program, which may have contributed to lowering the risk of second tumors; and (3) the results were obtained in a multicenter study (a condition that often impairs results from clinical trials).

MOPP/ABV/CAD chemotherapy with and without recombinant human granulocyte-macrophage colony stimulating factor in untreated, unfavorable prognosis Hodgkin's disease.

Seventeen consecutive patients with previously untreated poor prognosis Hodgkin's disease (clinical stage II and III with systemic symptoms, and stage IV) received 6 courses of aggressive chemotherapy, with (9 patients) and without (8 patients) the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Chemotherapy (MOPP/ABV/CAD regimen) included full doses of nitrogen mustard, lomustine (CCNU), vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine and bleomycin, and was administered between days 1 and 15 of each course. Course were planned for 28-day intervals. rhGM-CSF was given at a dose of 5 micrograms/kg/day subcutaneously from day 16 to 26 of each course. With cytopenia (i.e. white blood cell, WBC, count < 3.0 x 10(9)/L and/or platelet count < 100 x 10(9)/L) delaying courses was preferred to administering reduced drug dosages. Substantial delays (ranging from 7 to 28 days) in delivering cytostatics were necessary between 70% of courses. The cumulative mean number of days for which the courses had to be delayed before completing the 6 MOPP/ABV/CAD courses was 57. The percentage of planned doses of cytotoxic drugs (nitrogen mustard, melphalan, epidoxorubicin, procarbazine) actually administered was 92%. Causes of treatment delay were presented by leucopenia in 82% and by leuco-thrombocytopenia in 23% of the courses. The WBC nadir was constantly encountered at day 20-21 following completion of courses, and slightly worsened with subsequent courses. The decrease in platelet values was milder than that in WBC counts. There were no differences in any of the above parameters between patients treated with MOPP/ABV/CAD alone or followed by rhGM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive necrotic myelopathy as a paraneoplastic syndrome: report of a case and some pathogenetic considerations.

Progressive necrotic myelopathy is a syndrome characterized by a spotty necrotic degeneration of the whole spinal cord in both anterior and posterior horns. This syndrome was recorded in a man suffering from a lymphoplasmatocytoid lymphoma. Whilst the usual evolution of this neurological syndrome is inexorably fatal, our case had a better outcome, due to the good response of the neoplasm to therapy. Progressive necrotic myelopathy is an uncommon complication of cancer, but it is probably incorrectly recognized in a number of cases. Two possible pathogenetic hypotheses are suggested: an autoimmune or an infective mechanism.

[Spontaneous remission of visceral metastases of hypernephroma after nephrectomy. Description of a case and review of pathogenetic hypotheses]. / Remissione spontanea di metastasi viscerali da ipernefroma in seguito a nefrectomia. Descrizione di un caso e rassegna delle ipotesi patogenetiche.

We describe an absolutely spontaneous regression of visceral metastases from a renal carcinoma, following nephrectomy, in a 46 years old patient, who is at present in a complete uninterrupted remission for 39 months. After a literature review we point out the rarity of this event and emphasize its absolute spontaneity. Moreover, we suggest some considerations about the possible pathogenetic mechanisms of this unexpectedly positive outcome. Between these, because of the strongly positive psychologic attitude of the patient, the psycho-neuro-immunologic one is suggestive.

[ProMACE-MOPP vs. ProMACE-CytaBOM polychemotherapies in the treatment of large-cell and unclassifiable non-Hodgkin's lymphomas]. / Polichemioterapia ProMACE-MOPP vs ProMACE-CytaBOM nel trattamento dei linfomi non-Hodgkin a grandi cellule e inclassificabili.

The results of two distinct and successive clinical pilot studies investigating feasibility of aggressive chemotherapy in large cell and unclassified non-Hodgkin's lymphomas are reported. In the first study (1986-87) the ProMACE-MOPP chemotherapy (P-M), a 2nd generation regimen, was administered to 10 patients, whereas in the second study (1987-88) the ProMACE-CytaBOM schedule (P-C), a 3rd generation regimen, was administered to 13 patients. The clinical and prognostic features of the two groups of patients were quite comparable, the only difference being the different follow-up times (median: 43 vs 26 months). The number of complete remissions, freedom from relapse and overall survival were slightly better in the P-M group, with-out a statistically significant difference, despite the longer follow-up time. Hematological toxicity was higher in the P-M study, while gastrointestinal (mucositis, hepatic transitory damage) and neurological toxicity (peripheral neuritis) were somewhat lower. In conclusion, the P-M regimen is worth considering for the treatment of high grade malignant lymphomas, although it was not recently designed and is not widely used at present.

A plea to overcome the concept of "staging" and related inadequacy in multiple myeloma.

From a retrospective multivariate study on 107 multiple myeloma (MM) patients, serum beta 2-microglobulin (beta 2M) proved to be the best prognostic discriminator, better than each of the currently used staging systems (Durie and Salmon's [DS], Merlini, Waldenström and Jayakar's [MWJ] and the British Medical Research Council's [BMRC]). The predictive ability of each staging system is better improved by combining consideration of beta 2 M as a continuous rather than a binary variable (even at its best prognostic cut-off). The combination of BMRC with beta 2 M demonstrated the highest prognostic value, followed by those involving DS or MWJ. Ease and measurability of clinical parameters at diagnosis, parametric type of statistical model assumed for description of survival, and supply of direct estimate of expected survival are the characteristics of the MWJ system that suggest it is best able to integrate beta 2 M correctly in a prognostic index. The basic concepts and the clinical use of the available staging systems for MM are criticized along the following lines: a) the need to include new and homogeneously weighted parameters in future prognostic systems -b) the lack of direct correspondence between treatment requirements (according to stage) and available therapeutic resources -c) evidence of the rough stratification of the actual survival expectancy, as permitted by the current staging systems. A direct, and as accurate as possible estimate of prognosis--based on easy and measurable parameters evaluable at diagnosis--should replace the current classification of patients according to stages. This estimate should mark the clinical evaluation at diagnosis, should flexibly indicate treatment even according to different protocols or centers, and should allow very accurate statistical corrections for different survival expectancy at diagnosis when evaluating different treatments in clinical trials.

The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature.

Seventy-six patients with primary gastric non-Hodgkin's lymphomas (PGL) were diagnosed, and 75 were treated between 1975 and 1985. According to the Working Formulation 22 patients had low-grade malignant histologic subtypes, 27 intermediate-grade, and 27 high-grade. Twenty-four cases were diagnosed by endoscopic biopsies, 52 through laparotomy biopsies. Forty-five underwent subtotal or total gastric resection; seven were considered unresectable at laparotomy; 23 did not undergo surgery because of the high operative risk, mainly due to advanced age and coexisting diseases; and one died of myocardial infarction a few days after admission, before starting therapy. All patients who did not undergo laparotomy were staged with bipedal lymphangiography or abdominal ultrasonography and/or computed tomography. Stage, evaluated according to the criteria of Musshoff, was I or II1 in 16 cases, II2 in five, and IV in the remaining 55. Treatment modalities included surgery (S), chemotherapy (CT), radiotherapy (RT), and combinations thereof in the following proportions: only S in ten cases, S + CT in 32 cases, S + RT in one case, S + CT + RT in two cases, CT only in 25 cases, CT + RT in five cases. No substantial differences in response to therapy and in survival were found in relation to the different treatments. Ten-year survival was 43% in Stage I or II and 20% in Stage IV. Of the 45 resected patients, five postoperative deaths were recorded (11%). No bleeding or perforations were observed in the 30 unresected patients, and survival of such cases compared with that of the resected ones. These findings, together with data from the literature, suggest that some of the advantages claimed for surgery in PGL (debulking and abatement of the risk of perforation or hemorrhage during CT or RT) have been overestimated in relation to the intrinsic surgical risk and to the possibility of anticancer therapy. Gastric resection may still be unavoidable as a diagnostic procedure in a minority of cases and may represent the primary therapeutic procedure in clinically assessed early-stage and low-risk patients, but it cannot be considered mandatory whenever possible merely for debulking purposes or to obviate possible perforation or hemorrhage. The CT and/or RT can be effective in unresected and even bulky cases, providing minimal risk of severe hemorrhage or perforation.

Night sweats in Hodgkin's disease. A manifestation of preceding minor febrile pulses.

The authors verified the hypothesis regarding an unawareness of possible febrile alterations during night sleep in patients with Hodgkin's disease who complain of night sweats as their only symptom. In these patients, body temperature was monitored by means of a 0.01 degrees C-sensitive linear transducer coupled with a digital multimeter. The palm of the hand (after it was passively closed in a fist by a full bandage) was the body site where temperature measurement was found to be most comfortable for a sleeping patient and independent of movements during sleep. A good correlation was found between the hand temperature taken with this technique and oral temperature. Of six patients with sweating as their only symptom, sweating recurred during the night in four and during the afternoon in the other two. In all patients sweating was preceded by a critical 0.5 to 1.5 degrees C increase in hand temperature, which took place no more than 30 minutes before sweating. Those with nocturnal sweats awakened during the subsequent sweating-related, rapid temperature decrease. These results are consistent with the occurrence of slight unperceived febrile pulses that precede sweating. The only peculiarity of night sweats consists in the higher probability that a preceding slight temperature rise may not be perceived by a sleeping patient, who is more likely to be awakened by the discomfort of the subsequent sweating. This would also explain the small prognostic significance of these sweats, which is the same as that of the preceding fever. These results are discussed in light of the increasing clinical evidence that patients with Hodgkin's disease are often affected by an instability of the thermoregulatory hypothalamic centers.