María-José Terol

Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma.

PURPOSE Variables used to build up the International Index for aggressive lymphomas (age, performance status, stage, extranodal involvement, and lactic dehydrogenase [LDH]) are also important in low-grade lymphoma. To assess the prognostic value of this index in low-grade lymphoma, we have applied it to a series of 125 patients. PATIENTS AND METHODS One hundred twenty-five patients with low-grade lymphoma who were diagnosed at a single institution over a 20-year period and treated with standard chemotherapy were studied. End points of the study were response to therapy and survival according to the International Index. In addition to the International Index, main initial and evolutive variables were evaluated. Univariate and multivariate methods were used. RESULTS After applying the International Index, the patients divided into four risk groups: low (36% of cases), low-intermediate (32%), high-intermediate (20.8%), and high (11.2%), with complete response (CR) rates in the four groups being 60%, 35%, 23%, and 21%, respectively. Ten-year overall survival rates for the risk groups were as follows: low, 73.6%; low-intermediate, 45.2%; high-intermediate, 53.5%; and high, 0% (P < .001). When the International Index was included in a multivariate analysis, along with the main initial variables, International Index (P < .001) and sex (male, worse) (P = .038) were the only parameters related to survival. When response to therapy was also included, achievement of CR (P < .0001) and International Index (P < .001) were the most important factors. In patients who achieved a CR, the International Index was the only parameter related to survival (P = .051). The results were the same when the International Index was applied to the subset of 107 patients with follicular lymphoma. CONCLUSION In this study, the International Index has been found to be an important prognostic tool in low-grade lymphomas. Such an index could be used to predict prognosis not only in aggressive, but also in low-grade lymphomas.

CNS involvement in mantle-cell lymphoma

PURPOSE In non-Hodgkins lymphomas, CNS involvement is highly dependent on the histology of the lymphoma. Mantle-cell lymphoma (MCL) is a lymphoma type with distinctive histologic, biologic, and clinical features in which CNS involvement has only been rarely described. The purpose of this report is to describe the incidence, clinical characteristics, and outcome of CNS infiltration in patients with MCL seen at a single institution. PATIENTS AND METHODS Twenty-two patients with MCL, who account for 6% of all patients with nodal lymphomas diagnosed and monitored at a university hospital from 1987 to 1994, were studied. Analysis of the incidence of CNS involvement by the disease was performed. RESULTS Five of 22 patients (22%; exact 95% confidence interval [CI], 7.8% to 45.4%) with MCL developed CNS involvement at a median of 18 months (range, 6 to 59) from diagnosis. All of these patients presented with poor MCL histologic subtypes and advanced disease. When the CNS infiltration became apparent, all of the patients displayed neurologic signs and had lymphoid cells consistent with the diagnosis of MCL in the CSF. In most of the cases, CNS infiltration was part of resistant disease or generalized relapse and had an ominous significance. CONCLUSION The incidence of CNS involvement in MCL might be higher than previously recognized. The frequency of CNS infiltration in MCL deserves to be investigated in other series and, if a high incidence is confirmed, the risk factors, mechanisms, and clinical implications of such a complication should be further studied.

Expression of the adhesion molecule ICAM-1 in non-Hodgkin's lymphoma: relationship with tumor dissemination and prognostic importance.

PURPOSE To study the expression of intercellular adhesion molecule-1 (ICAM-1) by non-Hodgkins lymphomas and to assess its correlation with disease extension and prognosis. PATIENTS AND METHODS ICAM-1 (CD54-IOL54) expression was studied in 70 patients (35 male/35 female; median age, 56 years) with non-Hodgkins lymphoma from a single institution. Immunostaining was performed using a streptavidine-biotin alkaline phosphatase method and ICAM-1 expression was evaluated in a semiquantitative manner. The histologic distribution of the cases was the following: small lymphocytic, five cases; follicular, 14; mantle cell, five; diffuse large cell, 41; and T lymphoblastic, five. Forty patients (57%) were in stage IV, bulky disease was observed in 25 patients (36%), and extranodal involvement in 48 patients (69%). RESULTS ICAM-1 expression was negative (-) in 14 patients (20%), weak (+) in 21 (30%), positive (++) in 30 (43%), and strongly positive ( ) in five (7%). No significant relationship was found between ICAM-1 expression and the lymphoma histologic subtype. Patients with negative or weak ICAM-1 expression had more frequently disseminated (stage IV) disease (74% v 40%; P = .007), extranodal involvement (86% v 51%; P = .004), and bone marrow infiltration (57% v 26%; P = .015) than the remainders. Positive ICAM-1 patients had survival rates significantly better than those in whom ICAM-1 was negative or weakly expressed [2-year overall survival: 77% v 50%, respectively; P < .025]. In a multivariate study, ICAM-1 (P = .005) maintained, along with histologic subtype (P = .001) and the international prognostic index (IPI) (P = .056), its importance for predicting survival. Finally, when the group of aggressive non-Hodgkins lymphoma patients was analyzed, ICAM-1 expression inversely correlated with advanced stage (P = .025), extranodal involvement (P = .01), and bone marrow infiltration (P = .01), complete response (CR) achievement (65% v 32%; P = .025), and overall survival (70% v 26% at 2 years; P < .005). CONCLUSION In lymphoma patients, ICAM-1 expression correlates with lymphoma dissemination and is useful to assess prognosis.

An assessment of the clinicohematological criteria for the accelerated phase of chronic myeloid leukemia.

In order to assess the relative importance of the clinicohematological features most commonly associated with the accelerated phase (AP) of chronic myeloid leukemia (CML) in 175 consecutive patients, 12 variables generally considered as indicating AP were analyzed for their predictive value for blast crisis (BC) appearance in less than 1 yr. At the time of analysis, 118 patients had died and 104 had developed BC. At univariate study, 6 features were associated with a significantly higher BC‐probability: poor performance status (ECOG score >2), unexplained fever/sweats, severe bone pain, progressive splenomegaly despite adequate therapy, blood basophils (>20%) and peripheral blasts (6–12%). At logistic regression, only bone pain and blood blasts (6–12%) retained their prognostic importance; the relative risk of unexplained fever/sweats and progressive splenomegaly was also clinically relevant. One‐year BC‐probability from the appearance of 1 or more of the above features was 77.3% (95% CI: 66–86.6) and 100% since all 4 were observed. Finally, at least 1 of the 4 features was present prior to death in 6 of 7 patients dying from CML‐related causes while not in BC. AP can be defined by the appearance along CML evolution of 1 or more of the 4 above‐mentioned clinicohematological features.

Low-Grade Lymphoma: Clinical and Prognostic Studies in a Series of 143 Patients from a Single Institution

Clinical and prognostic studies were carried out in a series of 143 patients with low-grade (small-lymphocytic, follicular small cleaved cell, follicular mixed small- and large-cell) lymphoma. After treatment with alkylating agents (21.5% cases), combination chemotherapy (73.3%) or other therapies (5.2%), complete response (CR) was obtained in 40.7% of cases and partial response (PR) in 43.7%. The stage of the disease was the most important factor for response. With a median follow-up of 6.5 years, 48.0% (95% Cl: 37.5-58.5) of patients were alive 10 years after diagnosis. Among the initial parameters, advanced stage. B-symptoms, poor performance status, nodal involvement > 3 sites, extranodal involvement > or = 2 sites, WBC count > or = 10 x 10(9)/L, leukemic expression, high serum LDH levels, and bone marrow infiltration were all related to survival; treatment modality, however, had no influence on survival. In the multivariate analysis, stage (p = 0.008) and age (p = 0.053) were the most important prognostic factors. When considering response to therapy, both CR (p < 0.001) and PR (p = 0.003) emerged as the most important predictive variables, with only the absence of B-symptoms retaining its prognostic significance (p = 0.014) among the other parameters. In addition, in CR patients the duration of the response (< or = 1 year vs. > 1 year) was the most significant parameter for survival (p < 0.001). Finally, the initial stage (p = 0.011) and the histologic subtype (those patients with follicular mixed lymphoma relapsing less frequently than the others) (p = 0.052) were the only significant factors for relapse.

Presenting features, natural history, and prognostic factors in localized non‐Hodgkin's lymphomas: analysis of 117 cases from a single institution

Abstract:  Clinical features and prognostic factors were analyzed in a series of 117 patients with localized non‐Hodgkins lymphoma (stage I‐II). Median age of the patients was 53 years and 52% were men; 22% had a lymphoma of low‐grade histology and one‐third presented with extranodal involvement. Eighty percent of the patients achieved a complete response (CR); stage of disease and histology were revealed as the most important factors for response. When analysis was restricted to intermediate/high‐grade cases, stage showed a predictive value for response. With a median follow‐up of 4.5 years, median overall survival was 12.0 years, with 73% and 62.5% of patients being alive at 5 and 10 years, respectively. Main initial parameters significantly related to a shorter survival were intermediate/high‐grade histology, stage II, poor performance status, bulky disease, high serum LDH levels, increased ESR, and advanced International Index. In the multivariate analysis, stage, histology and performance status (PS) were statistically significant. Among intermediate/high‐grade lymphoma patients, stage and PS provided prognostic value for survival. Twenty‐six patients relapsed after CR; median survival after relapse was 2.7 years. Stage (I vs II) was the only predictive variable for relapse in both the whole series and the intermediate/high‐grade subset.

Using the Lymph2Cx assay for assessing cell-of-origin subtypes of HIV-related diffuse large B-cell lymphoma

Maria Joao Baptista , Gustavo Tapia, Mireia Morgades, Josep Muncunill, Ana-Mar ıa Mu~ noz-Marmol, Silvia Montoto, John G. Gribben, Maria Calaminici, Antonio Martinez , Blanca Gonzalez-Farre, Ivan Dlouhy, Eva Gonz alez-Barca, Mar ıa-Jos e Terol, Pilar Miralles, Miguel Alcoceba, Ferran Vall-Llovera, Javier Briones, Pau Abrisqueta, Eugenia Abella, Mariano Provencio, Carlos Garc ıa-Ballesteros, Jos e-Mar ıa Moraleda , Juan-Manuel Sancho, Josep-Maria Ribera , Jos e-Luis Mate and Jos e-Tomas Navarro Department of Hematology, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute (IJC), Institut Germans Trias i Pujol (IGTP), Universitat Aut onoma de Barcelona, Badalona, Spain; Department of Pathology, Hospital Germans Trias i Pujol, Universitat Aut onoma de Barcelona, Badalona, Spain; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Department of Pathology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; Department of Hematology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; Department of Hematology, ICOHospital Duran i Reynals, L’Hospitalet de Llobregat, Spain; Department of Hematology and Oncology, Hospital Cl ınic Universitari de Val encia, Valencia, Spain; Department of Infectious Diseases, Hospital Gregorio Mara~ n on, Madrid, Spain; Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain; Department of Clinical Hematology, Hospital Universitari Mut ua de Terrassa, Terrassa, Spain; Department of Hematology, Hospital de la Santa Creu i Sant Pau, Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain; Department of Hematology, Hospital Vall d’Hebr on, Barcelona, Spain; Department of Hematology, Hospital del Mar, Barcelona, Spain; Department of Medical Oncology, Hospital Universitario Puerta De Hierro, Majadahonda, Spain; Department of Hematology, Hospital Arnau de Vilanova, Valencia, Spain; Department of Hematology, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain