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Biomedical subjects

V M Lauta

Publications and source records attributed to V M Lauta.

At least 19 recordsLinked to original sources
PubMed2002

Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients.

BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients, we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G-CSF) regimen which, in a national multicenter trial, induced good complete response (CR) and relapse-free survival rates with only moderate toxic effects. Here we report a prospective, multicenter, randomized trial comparing the efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS AND METHODS: From February 1996 to June 2001, 306 consecutive previously untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and 148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively. Hematological and non-hematological toxicities were similar in both treatment groups. CONCLUSIONS: Our data show that extending induction treatment with the VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or provide a more durable remission.

Aged↗
PubMed2001

Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data.

Study of the network of cytokines has helped identify cell growth factors in multiple myeloma. Plasma cells themselves may produce autocrine interleukin 6 (IL-6) while IL-6 production by bone marrow stromal cells may operate a paracrine mechanism. Involvement of IL-6 in multiple myeloma is indicated by its ability to induce the differentiation of myeloma plasmablasts into mature malignant plasma cells. Differential diagnosis between multiple myeloma and monoclonal gammopathies of undetermined significance (MGUS) is generally based on clinical and laboratory parameters. Nevertheless, evaluation of the serum level of IL-6, C reactive protein, soluble IL-6 receptor, soluble IL-2 receptor together with the activity exerted by IL-3 and IL-4 on some cellular subsets constitutes an additional element in the differential diagnosis of border-line cases. Serum levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R) and the expression of membrane-bound IL-2 receptors, both on bone marrow plasma cells and on peripheral blood mononuclear cells are correlated with disease activity and disease stage. In addition, IL-6 and sIL-6R serum levels correlate with the duration of survival, as high values at the time of diagnosis correlate with short duration of survival.

Cytokines↗
PubMed2000

Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.

PURPOSE: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. PATIENTS AND METHODS: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). RESULTS: In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). CONCLUSION: Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.

Adult↗
PubMed2000

CEOP-B/VIMB vs. promace-CytaBOM in the treatment of intermediate or high grade non-Hodgkin's lymphoma: A randomised multicenter study of Southern Italy Cooperative Group.

From January 1992 to December 1995, 129 patients with previously untreated non-Hodgkin's lymphoma were randomised in a phase III multicenter trial to receive CEOP-B/VIMB or ProMACE-CytaBOM. Eligibility criteria included intermediate or high grade lymphoma (follicular large cell, diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic) with an Ann Arbor stage II bulky, III or IV. All patients entered into the study were considered evaluable according to intent to treat analysis. At a median follow-up of 60 months there were no significant differences between the treatment response rates [82% (60%CR) for CEOP-B/VIMB vs. 81% (69% CR) for ProMACE-CytaBOM]. Conversely, with regard to disease-free survival, a significant difference was observed between the two treatment arms (42% for CEOP-B/VIMB vs. 24% for ProMACE-CytaBOM at 5 years; p=0.046). However, this difference did not translate in a significant difference in overall survival (45% vs. 39% at 5 years). Moreover, when response rates and outcome were analysed for different prognostic subgroups according to International Prognostic Index, no significant differences were observed between the treatment groups. It is important to note that neither regimen was able to improve outcome of poor risk patients who fared badly with both treatments (median survival 9 and 8 months respectively). Toxicity was also similar in both treatments with grade 3-4 leukopenia observed in 39% and 47% of cases and grade 3-4 thrombocytopenia in 24% and 27% of cases respectively. In conclusion, in this study CEOP-B/VIMB was not superior to ProMACE-CytaBOM in aggressive lymphomas and the alternating strategy failed to improve outcome of poor risk patients in which newer more aggressive treatments are needed.

Adolescent↗
PubMed1999

Elderly aggressive-histology non-Hodgkin's lymphoma: first-line VNCOP-B regimen experience on 350 patients.

Age is a risk factor and a prognostic parameter in elderly aggressive-histology non-Hodgkin's lymphoma (NHL) patients. Several adapted chemotherapeutic regimens have recently been designed and tested on elderly patients. Several of these trials have shown that older aggressive-histology NHL patients can benefit from specific and adequate treatment capable of curing a percentage of these patients. Between January 1992 and September 1997, 350 previously untreated aggressive-histology NHL patients greater than 60 years of age were treated with a combination therapy including cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (VNCOP-B). Complete remission (CR) was achieved by 202 (58%) patients and partial remission (PR) by 87 (25%), whereas the remaining 61 (17%) patients were nonresponders. The overall response rate (CR + PR) was 83%. Clinical and hematologic toxicities were modest, because 71% of the patients received granulocyte colony-stimulating factor (G-CSF). The CR rates for the three age groups (60 to 69, 70 to 79, and >/=80 years) were similar: 61%, 59%, and 56%, respectively. At 5 years, the relapse-free survival rate was 65%, the overall survival rate was 49%, and the failure-free survival rate was 33%. In the multivariate analysis, prognostic factors associated with longer survival or longer relapse-free survival turned out to be localized disease stage (P =.001) and good performance status (P =.0002). Application of the International Prognostic Factor Index was significantly associated with outcome (P =.001). These data confirm on a large cohort of patients that the VNCOP-B regimen is effective in inducing good CR and relapse-free survival rates with only moderate toxic effects in elderly aggressive-histology NHL.

Aged↗
PubMed1999

An analysis of which subgroups of multiple myeloma patients, divided according to b(2)-microglobulin and plasma cell labeling index, benefit from high dose vs conventional chemotherapy.

BACKGROUND AND OBJECTIVE: The clinical advantage of high-dose therapy (HDT) over standard treatment for multiple myeloma (MM) patients has been recently assessed. Which patient subgroups benefit most from this approach is unclear. DESIGN AND METHODS: To address this issue, the outcome of 54 patients under 55 years old treated with HDT was compared with that of 101 age-matched controls selected from 390 patients who received standard melphalan and prednisone (MP) chemotherapy in a national multi-center trial (M90 protocol). RESULTS: The complete response (CR) rate was 50% in the HDT group compared to 5% in the MP group. Event-free survival (EFS) was three times longer for the HDT patients (median 34.5 vs 12.2 months, p<0. 0001), though the controls enjoyed a prolonged survival after relapse, and hence there was no statistically significant difference in OS. Overall survival (OS) was analyzed in relation to to two major prognostic factors: b(2)-microglobulin (b(2)-M) and bone marrow plasma cell labeling index (LI). HDT significantly improved OS in poor prognosis patients with a high LI (>1.2%), (median 49.5 vs 32.5 months, p<0.03), whereas it did not prolong OS in poor prognosis patients with high b(2 )-M (> 3 mg/L). INTERPRETATION AND CONCLUSIONS: In conclusion, HDT has a major impact on CR and EFS, and is the treatment of choice for patients with a high LI. Alternative strategies should be adopted in poor prognosis patients with high b(2 )-M.

Antineoplastic Agents↗
PubMed1999

How do patients with aggressive non-Hodgkin's lymphoma treated with third-generation regimens (MACOP-B and F-MACHOP) fare in the long-term?

BACKGROUND AND OBJECTIVE: To examine the long-term clinical course and prognostic factors of patients with advanced aggressive non-Hodgkin's lymphoma (NHL) treated with third-generation regimens as front-line chemotherapy. DESIGN AND METHODS: A total of 348 patients aged <60 years received MACOP-B or F-MACHOP regimen between September 1988 and August 1993 for advanced stage aggressive NHL. RESULTS: Of these, 249 (71.5%) obtained a complete response (CR); 65/249 (26%) subsequently relapsed. The CR rates for MACOP-B and F-MACHOP were 70.5% and 72%, respectively, while the relapse-free survival rates (RFS) at 9 years were 66% and 74%, respectively. The overall survival rate at 9 years was 61% for MACOP-B and 67% for F-MACHOP patients. Of the relapses, 78.5% were early (<24 months) and 21.5% late. Eleven out of 65 (17%) patients are in continuous second CR with a median follow-up of 45 months; most of them have been salvaged with high-dose therapies. The validity of the International Prognostic Index was confirmed in long-term analysis. INTERPRETATION AND CONCLUSIONS: With a 9-year RFS, it is possible to consider cured 50% of the patient with aggressive NHL treated with a third-generation regimen. About a quarter of the CRs relapse and late relapse occurs in roughly 20% of all relapsed patients. In these patients high-dose chemotherapy followed by autologous bone marrow or hematopoietic stem cell transplantation seems to be a very reliable approach in terms of long-term second CR. Finally, the IPI score maintains its pivotal role in terms of stratifying patients according to different risk subsets also in long-term analysis.

Adolescent↗
PubMed1999

Erythrocytes stored in CPD SAG-mannitol: evaluation of their deformability.

The erythrocytes deformability of three blood samples coming from healthy donors has been evaluated by Laser-assisted Optical Rotational Cell Analyzer (LORCA). Blood samples were stored in CPD SAG-mannitol. The study of progressive reduction in the Elongation Index (EI) during the preservation may be used as way of evaluation of erythrocyte vitality in stored blood samples.

Adenine↗
PubMed1999

Reduced deformability of erythrocytes as feature of congenital dyserythropoietic anaemia type II (HEMPAS).

In this study we report results regarding erythrocytes deformability in congenital dyserythropoietic anemia type II (HEMPAS) by the use of LORCA (Laser-assisted Optical Rotational Cell Analyzer). The reduced erythrocytes deformability observed in seven case of CDA II is caused by changes in the structure of glycoproteins due to the incomplete glycosylation of erythrocytic and erythroblastic membrane. Erythrocytes deformability (EI) was shown to be inversely related with mean corpuscular volume (MCV) and mean haemoglobin concentration (MCH).

Adolescent↗
PubMed1997

Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma.

Age is an important prognostic parameter, especially in patients with advanced high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and extensive therapy for any possible chance of cure. We investigated the potential of granulocyte colony-stimulating factor (G-CSF) for reducing myelotoxicity, which is the most important dose-limiting factor for chemotherapy. Between March 1993 and June 1995, 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative randomized comparative trial and treated with a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF was administered at 5 microg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days. Of the 158 patients registered for the trial, 149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone. The overall response rate was 81.5%, with complete response in 59%: 60% in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months (median 24 months), 68% of all complete responders were alive without disease in the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of 77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the controls (P = .00005). Clinically relevant infections occurred in 4 out of 77 (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but the difference was not statistically significant. Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients, and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity, CR rate, and relapse-free survival curve.

Age Factors↗
PubMed1997

Conventional induction treatments do not influence overall survival in multiple myeloma.

A retrospective analysis was performed on two subsequent myeloma patient series treated with the same conventional induction treatments, melphalan and prednisone or alternating VMCP/VBAP: 273 were enrolled in the multicentre M83 trial (M83 trial group) from 1983 to 1986; 160 were referred to a single institution (Haemat. To group) from 1986 to 1994. Response to treatment was very similar in the two groups (53% v 50.3%). Remission duration curves merely overlapped (median 20 v 21 months). However, overall survival was significantly longer in the Haemat. To group (43.2 v 33 months, P < 0.04). This difference was due to a prolonged period from relapse or progression to death (21 v 8 months, P < 0.01; 20.8 v 7 months, P < 0.009). Prolonged survival was also observed in poor-prognosis patients with a serum beta2-microglobulin level > 3 mg/l, in the Haemat. To group (31.8 v 24.2 months, P < 0.04). The same induction treatments produced almost identical response rate and remission duration in both groups, but overall survival was 10 months longer for one group. However, it could be argued that treatment salvage modalities and support therapies have been improved in a decade. Lastly, induction treatments did not influence overall survival.

Adult↗
PubMed1995

Interferon and chronic myelogenous leukaemia.

Interferon (IFN) is widely employed in the therapy of chronic myelogenous leukaemia because of its ability to exert the antiproliferative activity on leukaemic haematopoietic progenitors and for the expression for IFN-alpha receptors by peripheral blood leukaemic cell surfaces. There is no difference between recombinant IFN alpha 2b and alpha 2a regarding their efficacy in the treatment of Ph-positive CML patients. Either no randomized studies or the randomized ones show a superior effectiveness of IFN given as single agent in the induction treatment to that one of chemotherapy regarding the complete cytogenic response percentage. The ability of IFN-gamma to induce the expression of adhesion molecules such LFA 1 and ICAM 1 on peripheral blood leukaemic cell surfaces may suggest its use in the induction therapy of CML patients. Other than, a superior effectiveness of combined therapy including interferon and chemotherapy agents compared to chemotherapy alone has also been found. Finally no large series of trials to study the IFN efficacy both as second line treatment and maintenance therapy have been carried out.

Antineoplastic Agents↗
PubMed1995

Interferon and multiple myeloma.

In vivo and in vitro studies are used to investigate interferon's use treating human multiple myeloma. In vitro studies demonstrate that the production of monoclonal immunoglobulin by myeloma plasma cells is reduced by alpha interferon; furthermore, interferon alpha seems to inhibit myeloma cell lines development. In vivo studies using interferon in the treatment of multiple myeloma experimentally reproduced in mice show low percentages of mortality among mice treated with high doses of interferon as opposed to high mortality among those treated with low doses. Clinical trials to evaluate the interferon efficacy in the treatment of human multiple myeloma demonstrate that the therapy of previously untreated patients using interferon is not useful because the response rate is lower than that of chemotherapy. There is no homogeneity of results of combined chemotherapy plus interferon as induction treatment of previously untreated patients. Homogeneous results are also not obtained using interferon alone or in combination with chemotherapy as a second induction treatment of relapsed patients. However, interferon seems to be effective as maintenance therapy of a response obtained with previous chemotherapy.

Animals↗
PubMed1995

Long-term results regarding the use of recombinant interferon alpha-2b in the treatment of II type mixed essential cryoglobulinemia.

Thirty-three patients with II type mixed essential cryoglobulinemia (MEC) were randomized into two groups: one to receive combined therapy including prednisone plus interferon, the other to receive prednisone therapy. Interferon was administered as induction treatment (3 Mu/day) and then as maintenance therapy (3 Mu three times a week). 83% of the combined therapy patients responded as opposed to 27% of the prednisone treated patients. Among the patients that responded to combined therapy, nine of them had a complete response, four a partial response, and two a minor response. None of the patients treated with prednisone therapy responded completely but only two had a partial and two a minor response. Four patients (three of combined therapy and one of prednisone therapy) showed proteinuria before the treatment which improved at the end of the induction therapy. Ten patients showed anti-HCV positivity which remained unchanged after the treatment. Three patients showed liver involvement secondary to cryoglobulinemia and an improvement of histological pattern after the induction with combined therapy. One patient showed an improvement of peripheral neuropathy after induction with the combined therapy. These data suggest the effectiveness of interferon given as induction and as maintenance treatment in the therapy of II type mixed essential cryoglobulinemia.

Antiviral Agents↗
PubMed1995

Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma.

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Adult↗
PubMed1994

Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma. Identification of a subset at high risk of treatment failure.

BACKGROUND: This study explores the ability of the combined detection of soluble IL-2 receptor (sIL-2r) and interleukin-10 (IL-10) to predict treatment failure in patients with aggressive non-Hodgkin's lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Serum levels of sIL-2r and IL-10 were measured serially in 93 patients with newly diagnosed aggressive NHL treated with four courses of a multiagent chemotherapy regimen. GM-CSF was administered subcutaneously in 39 of these patients from day +5 to day +18 after each chemotherapy course. RESULTS: Pretreatment levels of sIL-2r were greatly elevated in patients with NHL compared with control subjects (P < 0.001), significantly correlating with the Ann Arbor stage (P < 0.001) and beta 2-microglobulin (beta 2-m) concentrations (r = 0.552, P = 0.004). IL-10 was detected in 37 patients at diagnosis, with no correlation with clinicohematologic parameters, and was not detected in the control sample (P < 0.001). Cytokine and receptor levels progressively declined to normal ranges in responding patients, whereas they remained elevated in nonresponders. During administration of GM-CSF, the authors observed an increase of sIL-2r, whereas lower elevations were recorded for IL-10. However, on completion of the induction treatment, cytokine/receptor levels were comparable in patients with the same type of response, whether or not they had received GM-CSF. In the five patients who were investigated at relapse, the levels of sIL-2r, beta 2-m, and lactic dehydrogenase were found to be elevated. IL-10 concentrations were high in three of these patients: two already had detectable levels at presentation, whereas one tested positive only on recurrence. No single parameter was associated with response to therapy, but the combination of elevated IL-10 and sIL-2r concentrations greater than 3000 U/ml resulted in a subset of eight patients who failed induction chemotherapy (P < 0.001). In addition, six of eight patients with high IL-10 and beta 2-m concentrations greater than 3.3 mg/l had an unfavorable outcome (P = 0.003). A multivariate regression model was used to identify sIL-2r (P = 0.004) and beta 2-m (P = 0.043) as the covariates that amplified the prognostic ability of IL-10. CONCLUSIONS: sIL-2r and IL-10 measurements provide valuable information for better management of patients with NHL as markers to monitor disease activity and as prognostic indicators.

Adolescent↗
PubMed1994

Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma.

We investigated the prognostic significance of interleukin-10 (IL-10) and soluble interleukin-2 receptor (sIL-2r) levels in the pretreatment serum of 105 individuals with newly-diagnosed aggressive non-Hodgkin's lymphoma (NHL). Commercially available enzyme-linked immunoassay kits were used for cytokine and receptor measurements. Detectable levels of IL-10 were found in 42 (40%) patients at diagnosis, with no correlation with clinico-haematological parameters, but in no control samples (P < 0.001). Pretreatment concentrations of sIL-2r were markedly increased in individuals with NHL when compared to controls (2614 +/- 893 U/ml v 219 +/- 65 U/ml, P < 0.001), patients with stage III/IV presenting higher values than those with stage II disease (3885 +/- 1196 U/ml v 1732 +/- 646 U/ml, P < 0.001). No single parameter was associated with the achievement of complete remission, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subset of patients with a high probability of failing induction therapy (P < 0.001). Life-table analysis also indicated that patients with these characteristics have a significantly shorter event-free survival. In a multivariate analysis the combination of IL-10 with sIL-2r was found to have greater predictive strength than the combination of IL-10 with beta 2-microglobulin. We conclude that IL-10 and sIL-2r measurements can be expected to improve existing methods of risk assignment in aggressive NHL.

Adult↗