levoleucovorin and Lymphoma--Large-Cell--Anaplastic

Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive (ALK+ ALCL) is an aggressive CD30-positive T-cell lymphoma that exhibits a chromosomal translocation involving the ALK gene and the expression of ALK protein. No particular risk factor has been clearly identified for ALCL. ALK+ ALCL shows a broad morphologic spectrum, but all cases contain a variable proportion of cells with eccentric, horseshoe- or kidney-shaped nuclei often with an eosinophilic region near the nucleus (hallmark cells). Five morphologic patterns can be recognized. ALK+ ALCL occurs in young subjects (median age ∼35 years), with male predominance, and frequently presents at an advanced stage, with systemic symptoms and extranodal involvement. Near 40% of patients are low risk according to the International Prognostic Index (IPI). Overall, the prognosis of ALK+ ALCL is remarkably better than other T-cell lymphomas. The IPI and the PIT scores in general predict survival in patients with ALK+ ALCL. Standard first-line treatment for ALK+ ALCL consists of doxorubicin-containing polychemotherapy, which is associated with an overall response rate of ∼90%, a 5-year relapse-free survival of ∼60%, and a 5-year overall survival of 70%. Excellent results have been reported with a variety of anthracycline-based chemotherapy regimens including CHOP, CHOEP or MACOP-B. Consolidative high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) has also been evaluated in patients in first remission with favourable results, however, superiority to standard chemotherapy is unproven and this approach remains investigational. Following universally accepted guidelines for the treatment of failed aggressive lymphomas, HDC/ASCT can effectively salvage a proportion of patients with relapsed or refractory ALK+ ALCL. Recently, the development of novel therapies targeting CD30 and ALK appear promising.

Topics: Anaplastic Lymphoma Kinase; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma, Large-Cell, Anaplastic; Methotrexate; Prednisolone; Prednisone; Receptor Protein-Tyrosine Kinases; Stem Cell Transplantation; T-Lymphocytes; Translocation, Genetic; Vincristine

During the last few years, morphological, immunohistochemical, and genetic findings have placed anaplastic large cell lymphoma (ALCL) as a distinct clinicopathologic entity, and several reports have focused on the existence of different subtypes of the tumor. Particular attention has been paid to the ALCL-Hodgkin's-like (HL) subtype, which seems to be on the border between Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL). From September 1994 to July 1997, during the course of an Italian multicentric trial, 40 ALCL-HLs were randomized to receive as front-line chemotherapy MACOP-B (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin-a third-generation HG-NHL regimen) or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine-a scheme specific for HD). All patients with bulky disease in the mediastinum at diagnosis underwent local radiotherapy after the chemotherapeutic program. Complete response (CR) was achieved in 17 of the 19 (90%) patients who were treated with MACOP-B, and in 19 of the 21 (91%) patients who were administered ABVD. The probability of relapse-free survival, projected at 32 months, was 94% for the MACOP-B subset and 91% for the ABVD subset. The majority of patients with mediastinal bulky disease obtained CR (evaluated with 67Ga single photon emission computed tomography [SPECT]) after their radiotherapy. The present study suggests that ALCL-HL, in line with its borderline status, responds in an equivalent way to third-generation chemotherapy for HG-NHL and to conventional HD treatment in terms of both CR and relapse-free survival rates. However, as to the latter, a longer follow-up period may be needed before stating the absolute equivalence of the two regimens used.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Leucovorin; Lymphoma, Large-Cell, Anaplastic; Male; Mediastinum; Methotrexate; Middle Aged; Prednisone; Remission Induction; Survival Analysis; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vinblastine; Vincristine

During the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkin's-like/Hodgkin's-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkin's disease (HD).. From September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkin's lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively.. Complete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms.. The data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Fluorouracil; Humans; Leucovorin; Lymphoma, Large-Cell, Anaplastic; Male; Methotrexate; Middle Aged; Phenotype; Prednisone; Prospective Studies; Recurrence; Survival Rate; Vincristine

To compare efficacy of NHL-BFM-90 and CHOP-like courses in the treatment of anaplastic large cell lymphoma (ALCL).. Twenty-two patients with ALCL participated in the study. The diagnosis was made basing on the findings of clinical, device, morphological, immunohistochemical and molecular-genetic examinations with application of a panel of monoclonal antibodies to CD30, ALK, CD3, CD4, CDS, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA, Ki-67. 14 cases of 22 were negative by kinase of anaplastic lymphocytes (ALK-) and 8 were positive (ALK+). Mean age of ALK-ALCL patients was 39.6 +/- 4.1 years, of ALK+ALCL patients - 23.4 +/- 2.6 years. 14 patients were treated by the protocol NHL-BFM-90, 8 were initially treated with other schemes (CHOP, MACOP-B, BEACOPP and others). All 14 patients treated according to NHL-BFM-90 had ALCL stages III-IV with B-symptoms. 12 patients who completed treatment by the above protocol achieved complete remission after the forth course, 2 patients failed the treatment. Of 8 ALCL patients treated initially according to other schemes, a complete remission was achieved in 4 patients (2 had stage II). One of 4 patients with remission had recurrence. Four patients who had failed to achieve complete remission died of the disease progression.. ALCL occurs more frequently in young and middle-aged patients. The disease has an aggressive course with rapid generalization. For such processes it is more preferable to use a modified protocol NHL-BFM-90.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bleomycin; Cyclophosphamide; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large-Cell, Anaplastic; Male; Methotrexate; Middle Aged; Prednisone; Procarbazine; Remission Induction; Treatment Outcome; Vincristine

Topics: Adult; Albendazole; Anthelmintics; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Bleomycin; Cyclophosphamide; Cytomegalovirus Infections; Doxorubicin; Endemic Diseases; Ganciclovir; Gastritis; Humans; Immunocompromised Host; Immunosuppressive Agents; Leucovorin; Lymphoma, Large-Cell, Anaplastic; Male; Methotrexate; Oman; Prednisolone; Prednisone; Remission Induction; Strongyloidiasis; Vincristine

Sixty-nine anaplastic large cell lymphomas (ALCLs) were selected from an Italian comparative trial on MACOP-B and F-MACHOP. As no significant difference in effectiveness of the protocols emerged, they were considered homogeneously treated. The ALCLs were divided into two groups according to previously defined criteria: 41 were common type (ALCLs-CT) and 28 Hodgkin-related (ALCLs-HR). T-cell phenotype was most common (58%), while B-cell, null and hybrid forms accounted for 27%, 13% and 2%. Clinically, ALCLs CT and HR differed as to mean age (27 v 34.3 years) and presentation; all ALCLs-HR showed mediastinal involvement, with bulky disease in 57%, and more frequent occurrence in stage II. In contrast, ALCLs-CT showed mediastinal masses in 58.5%, infrequently revealed bulky disease (24%), and were not specifically associated to stage. Among the ALCLs-CT, 68.4% achieved complete remission (CR), 24.4% partial remission (PR), one (2.4%) was resistant to therapy, and two (4.8%) had fatal drug toxicity. Of the ALCLs-HR, 67.8% reached CR, 14.3% PR, and 17.9% did not respond. In CR, ALCLs-CT showed a greater tendency to relapse (32.1% v 14.2%). At present, 65.8% of ALCLs-CT and 67.8% of ALCLs-HR are alive with overall survival/disease-free survival averages of 31/27 and 29/24 months respectively. Our data emphasize that, independently of subtype, ALCLs benefit from the application of third-generation protocols for high-grade non-Hodgkin's lymphomas.

Topics: Adolescent; Adult; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Fluorouracil; Humans; Immunoenzyme Techniques; Ki-1 Antigen; Leucovorin; Lymphoma, Large-Cell, Anaplastic; Male; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Vincristine