Hagenbeek A, for the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group [ Univ Hosp, Utrecht, The Netherlands]
Maintenance of Remission with Human Recombinant Interferon Alfa-2a in Patients with Stages III and IV Low-Grade Malignant Non-Hodgkins Lymphoma
J Clin Oncol 16: 41-47, 1998
Interferon a is known to have significant activity in patients with low-grade malignant non-Hodgkins lymphoma [ NHL]. IFN a is also useful as maintenance therapy after tumor load has been reduced with chemotherapy in advanced low grade malignant NHL.
This study of 315 patients with stage III or IV low grade NHL received cyclophosphamide, vincristine and prednisone [CVP] every three weeks for 8 cycles followed by local radiotherapy and to IFN a-2a as maintenance.
Patients who received IFNa-2a had a more prolonged time to progression than control group. However, the two groups had similar overall survival rate.
Cole BF, Solal-Celigny P, Gelber RD, et al [ Dartmouth Med School, Lebanon, NH; Groupe dEtude des Lympphomes Folliculaires, Caen, France; Groupe dEtude des Lymphomes Folliculaires Creteil, France; et al]
Quality of Life-Adjusted Survival Analysis of Interferon Alfa-2b Treatment for Advanced Follicular Lymphoma: An Aid to Clinical Decision Making
J Clin Oncol 16: 2339-2344, 1998
This study is on quality of life adjusted survival analysis from Group dEtude des Lymphomes Folliculaires [GELF] comparing cyclophosphamide, doxorubicin, teniposide and prednisone [CHVP] with CHVP plus interferon –a-2b in a large group of patients with advanced low-grade follicular NHL.Although the combined regimen at a median follow up of 72 months had improved progression free survival and overall survival. The patient in this group had additional toxicity. In a sensitivity analysis CHVP plus IFN provided longer quality adjusted survival. The value of this benefit depends on individual’s relatives quality of life, the valuations for time with toxicity and time after disease progression.
Solal Celigny P, Lepage E, Brousse N, et al [ Groupe dEtude des Lymphomes Folliculaires, Caen, France; Groupe dEtude des Lymphomes Folliculaires, Creteil, France; Groupe dEtude Des Lymphomes Folliculaires, Lyon, France; et al]
Doxorubicin-Containing Regimen with or without Interferon Alfa-2b for Advanced Follicular Lymphomas : Final Analysis of Survival and Toxicity in the Groupe dEtude des Lymphomes Folliculaires 86 Trial
J Clin Oncol 16: 2332-2338, 1998
Interferon –a is known for its anti proliferative and induction of cell surface antigen on tumor cells.
This study with advance stage follicular lymphoma received cyclophosphamide, adriamycin, teniposide and prednisone [ CHVP ] alone [ 119 patients ] or with interferon [ 123 patients ]. Patients with CHVP interferon had significantly longer median overall survival than with CHVP alone. The adverse effect with IFN-a recipients were flu-like syndrome, neutropenia, thrombocytopenia, asthenia, fever increased serum transaminase.
Liu SY, Eary JF, Petersdorf SH, et al [Univ of Washington, Seattle; Fred Hutchinson Cancer Research Ctr, Seattle; Pacific Northwest Natl Lab, Richland, Wash]
Follow-up of Relapsed B-Cell Lymphoma Patients Treated with Iodine 131-Labeled Anti-CD20 Antibody and Autologous Stem-Cell Rescue
J Clin Oncol 16: 3270-3278, 1998
This study of 29 patients with relapsed Non Hodgkins Lymphoma [NHL] purged with monoclonal antibodies and complement were cryopreserved. Optimal 131I-anti-B1 myeloablative dose was delivered, marrow or stem cells were reinfused.
The overall survival rate at 4 years for patients with indolent lymphomas was 78% compared to 43% with aggressive lymphomas. Progression-free rates for patients with low-grade and with intermediate or high grade tumors were 51% and 20% respectively. Time to treatment failure after radio immunotherapy was longer than only other modality. The most common late complication was thyroid dysfunction.
Hasenclever D, for the International Prognostic Factors Project on Advanced Hodgkins Disease [Univ of Leipzig, Germany; et al]
A Prognostic Score for Advanced Hodgkins Disease
N Engl J Med 339: 1506-1514, 1998
Prognostic factors determine the outcome of patients with non-hodgkins lymphoma and identify a sub-group of patients who would benefit from treatment.
This study 5141 patients of advanced Hodgkins disease were analyzed for freedom from progression following combination chemotherapy with or without radiation.
The authors developed a prognostic scoring system for advanced stage Hodgkin’s lymphoma. The seven point scoring system included serum albumin < 4 gm/dl, haemoglobin < 10.5 gm/dl male sex, stage IV disease age > 45 years WBC > 15,000/ mm2. Lymphocyte count < 600 / mm2. The scoring system could identify patients with a more favorable prognosis and therefore be curable with less aggressive therapy but could not identify the poor prognostic group of patients with advanced hodgkin’s.
Blay J-Y, Conroy T, Chevreau C, et al [ Centre Leon Berard, Lyon, France; Centre Alexis Vautrin, Nancy, France; Centre Claudius Regaud, Toulouse, France; et al]
High-Dose Methotrexate for the Treatment of Primary Cerebral Lymphomas: Analysis of Survival and Late Neurologic Toxicity in a Retro-spective Series
J Clin Oncol 16: 864-871, 1998
The therapy of primary cerebral lymphoma [PCL] remains controversial, radiotherapy and for chemotherapy are the corner stores. The prognostic factors and the late neurotoxicity associated with such a therapy. For patients with PCL was identified in this study.
Patients younger than 60 years with good performance status and without increased lactate dehydrogenase had significantly improved survival. Patients who received chemotherapy and especially with high dose methotraxate had significantly improved survival, however, late neurologic toxicities was encountered especially if received after radiotherapy.
Abrey LE, De Angelis LM, Yahalom J [ Mem Sloan – Kettering Cancer Ctr, New York]
Long-term Survival in Primary CNS Lymphoma
J Clin Oncol 16: 859-863, 1998
Cranial radiotherapy and high dose cytarabine have yielded encouraging results in patients with primary cerebral lymphomas.
This study of 31 patients with PCL treated with combined modality were studied for long term disease control, survival and outcome.
The median disease free survival, relapse rate were better for combined modality however, late nerulogic toxicity especially in patients older than 60 years experience leukoencephalopathy within one year. Hence, less toxic treatments are needed, particularly for the elders.
Sandor V, Stark-Vancs V, Pearson D, et al [Natl Cancer Inst, Bethesda, Md; NIH, Bethesda, Md]
Phase II Trial Chemotherapy Alone for Primary CNS and Intraocular Lymphoma
J Clin Oncol 16: 3000-3006, 1998
Combined modality therapy for primary cerebral lymphoma [PCL] given optimal results especially in the younger patients.
This study of 14 patients who received aggressive chemotherapy with high dose methotrexate, thiotepa, leucovorin and vincristine were studied for response rate, survival and progression-fee survival.
Chemotherapy could induce high and durable remission in patients with PCL however neurological toxicity especially the elderly age group was evident.
Glick JH, Young ML, Harrington D, et al [ Univ of Pennsylvania Cancer Ctr, Philadelphia; Dana – Farber Cancer Inst, Boston; Univ of chicago; et al]
MOPP/ABV Hybrid Chemotherapy for Advanced Hodgkins Disease Significantly Improves Failure-free and Overall Survival: The 8-Year Results of the Intergroup Trial
J Clin Oncol 16: 19-26, 1998
This study of advanced Hodgkins disease stage III2A, IIIB, IVA or IVB or in first relapse after radiotherapy were assigned to sequential MOPP-ABVD or MOPP/ABV hybrid therapy.
The overall and failure-free survival were both significantly improved with the hybrid treatment then sequential MOPP/ABVP. The hybrid therapy was also associated with a lower incidence of acute leukemia and myelodysplasia. The editor does not think that the use of non – cross-resistant combination chemotherapy regimens whether given sequentially, alternatively or in a hybrid form have proved their worth and would advise the oncologist to use a regimen with which they are familiar and ABVD in optimal dose appears a reasonable choice.
McLaughlin P, Grillo-Lopez AJ, Link BK, et al, [Univ of Texas, Houston; IDEC, Pharmaceuticals Corp, San Diego, Calif; Univ of lowa, lowa City; et al]
Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program
J Clin Oncol 16: 2825-2833, 1998
The targeted therapy i.e. the chimeric monoclonal antibody to CD20 antigen is expressed on more than 90% of B-cell lymphomas and is one of new therapeutic modality.
This study of 166 patients with relapsed low grade or follicular lymphoma received chimeric anti CD20 antibody IDEC-C2B8, 48% of patients responded with with median time of progression of 13 months. The most common adverse effect were fever and chills.
The editor mentions that Rituximabs mechanism of action once attributed to traditional antibody – mediated processes, cellular cytotoxicity however, recent work suggests the antitumor effects of anti-CD20 is direct inhibition of B-cell proliferation and induction of nuclear DNA fragmentation with death via apoptosis since CD20 appears to function as a calcium channel. Anti CD20 mediated apoptosis may be related to changes in intracellular Ca2+ concentration. This novel mechanism of action intakes it a good alternative of combining with chemotherapy.
Coiffier B, Haioun C, Kettrer N, et al [ Centre Hospitalier Lyon-Sud, Pierre-Benite, France; Hopital Henri-Mondor, Creteil, France; Univeritat zu Koln, Germany, et al]
Rituximab [Anti-CD20 Monoclonal Antibody] for the Treatment of Patients with Relapsing or Refractory Aggressive Lymphoma: A Multicenter Phase II Study
Blood 92: 1927-1932, 1998
Rituximab is a chimeric monoclonal antibody that binds to CD20 antigen produces approximately 50% of responses in low grade or follicular B-cell lymphomas however there are other lymphomas which also express CD20 antigen. The role of Rituximab was studied by these investigators in these subgroup of lymphoma. Patients with DLCL mantle cell lymphoma [MCL] had 37% and 33% response rates to Rituximab with low toxicity profile.
The editor comments that such a impressive single agent response rate in DLCL and MCL requires further study in relapsed patients who are not eligible for any aggressive therapeutic approach.
Miller TP, Dahlberg S, Cassady JR, et al [ Univ of Arizona, Tucson; Southwest Oncology Group Statistical Center, Seattle; cleveland Clinic Found, Ohio; et al]
Chemotherapy Alone Compared with Chemotherapy Plus Radiotherapy for Localized Intermediate-and High-Grade Non-Hodgkins Lymphoma
N Engl J Med 339: 21-26, 1998
The standard therapy for clinically localized, i.e. stage I & II intermediate or high-grade non – Hodgkins lymphoma consists of doxorubicin containing chemotherapy regimen such as cyclophosphamide, doxorubicin, vincristine and prednisone [ CHOP].
This study has compared randomly stage I & II intermediate or high grade NHL to 3 courses [group I] of CHOP chemotherapy followed by local RT to 8 courses of CHOP [group2].
Estimated 5 year progression free survival was 77% for group I & 64% for group II and overall survival 82% & 72% respectively. Hence treatment with 3 courses if CHOP followed by local radiotherapy is superior to 8 courses of CHOP in this clinical study.
Mac Manus MP, Rainer Bowie CA, Hoppe RT [Peter MacCallum Cancer Inst, Melbourne, Australia; O Connor Hosp, San Jose, Calif; Stanford Univ, Calif]
What is the Prognosis for Patients who Relapse After Primary Radiation Therapy for Early- Stage Low-Grade Follicular Lymphoma?
Int J Radiat Oncol Biol Phys 42: 365-371, 1998
The therapy for early stage I & II low grade follicular lymphoma is radiotherapy. However, only 40% to 50% of such patients have a prolonged disease free survival.
Richaud PM, Soubeyran P, Eghbali H, et al [Regional Cancer Ctr, Bordeaux Cedex, France; Hopital de Haut-Leveque, Pessac, France]
Place of Low-Dose Total Body Irradiation in the Treatment of Localized Follicular Non-Hodgkins Lymphoma: Results of a Pilot Study
Int J Radiat Oncol Biol Phys 40: 387-390, 1998
Low-dose total body irradiation [LD-TBI] has been shown to be effective first line treatment in advanced-stage low grade NHL. The initial results of this form of therapy in this study has revealed excellent clinical tolerance, a very high rate of complete remission in localized disease. Whether these improved treatment results translate into long term disease free survival is yet to be determined.
Moog F, Bangerter M, Diederichs CG, et al [Univ of Ulm, Germany]
Extranodal Malignant Lymphoma: Detection With FDG PET Versus CT
Radiology 206: 475-481, 1998
The exact staging technique for lymphoma by noninvasive methods to detect disease in spleen, liver and bone marrow are not clear. This study compares PET versus CT scan. 42 lesions were detected by both PET & CT & were confirmed with biopsy results . Another 24 results were seen on PET, 15 of which were verified by biopsy, MRI scintigraphic, or follow up results. Seven lesions not detected by FDG PET were identified on CT. 6 of which were confirmed by biopsy or follow-up. Findings on PET resulted in changes in tumor staging in 13 patients. Functional imaging with FDG PET can provide important information for diagnosis of untreated lymphoma and can assess liver, spleen and bone marrow involvement however further clinical studies would be required.
Paulli M, Berti E, Boveri E, et al [ Univ of Pavia, Italy; Univ of Milano, Italy: IRCCS Policlinico, Milano, Italy; et al]
Cutaneous CD30+ Lymphoproliferative Disorders : Expression of bcl-2 and Proteins of the Tumor Necrosis Factor Receptor Superfamily
Hum Pathol 29: 1223-1230, 1998
This study included 25 patients who had CD30+ cutaneous lymphoma and analyzed expression of CD95 and other proteins associated with apoptosis nerve growth factor receptor [NGF-R], the anti-apoptotic protein bcl-2. Analysis revealed consistent expression of CD95 but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from regressing lymphomatoid papulosis [LyP] and nonregressing CD30+ lymphomas. Levels of bcl-2 were low in LyP and high in pleomorphic CD30+ lymphomas. The increased expression of bcl-2 by tumor cells that did not regress suggests the possibility that this oncoprotein may actually protect tumor cells from apoptosis with CD30+ cutaneous lymphomas.
V.Diehl, J Franklin et al (Cologne Univ, Loeln, Germnay; Frankfurt Univ, Germany)
Dose Escalation of BEACOPP Chemotherapy for Advanced Hodgkin’s Disease in Hodgkin’s Disease increase trial of German Hodgkin’s Lymphoma Study Group (GHSG)
Proceedings on 30th Annual meeting of ASCO, 20th – 23rd May, 2000, New Orleans.
This is a three armed study, HD9 trial had patients of Hodgkin’s Disease unfavourable CS IIB/IIA and CS IIIB/IV who received two dose schedules of BEACOPP (baseline +escalated) were compared with COPP/ABVD. Both BEACOPP variants were significantly superior to COPP/ABVD regarding failure free survival and overall survival. Escalated BEACOPP has considerable haematologic toxicity requiring dose reduction in subsequent courses but the total dose was still considerable higher than baseline. The final analysis is pending.
Foss H-D, Reusch R, Demel G, et al [Free Univ of Berlin]
Frequent Expression of the B-Cell-Specific Activator Protein in Reed-Sternberg Cells of Classical Hodgkin’s Disease Provides Further Evidence for Its B-Cell Origin
Blood 94:3108-3113, 1999
The cellular origin of classical Hodgkin’s disease remains unknown.
The transcription factor B-Cell-specific activator protein [BSAP] is specific for B-cells and influences B-cell functions. 80% of the classic Hodgkin’s disease specimens and all of the nodular, lymphocyte-predominant contained BSAP suggesting B-cell origin. This could be used to differentiate anaplastic large cell lymphoma from the classic Hodgkin’s disease.
Karavattathayyil SJ, Kalkeri G, Liu H-J et al (Tulane Univ., New Orleans, La)
Detection of Hepatitis C Virus RNA Sequences in B-cell Non-Hodgkin Lymphoma.
Am J Clin Patho. 113: 391-398, 2000.
Infection with hepatitis C virus (HCV) trigger a variety of aberrant immune phenomena such as autoimmune disease, proliferation of reactive lymphoid aggregates in bone marrow and cryoglobulinemia. This study of 31 patients with B-cell NHL. The reverse-transcription double polymerase chain reaction (RT-PCR) and immunohistochemistry, could detect HCV infection and B-cell NHL association. Whether HCV infection is involved in the pathogenesis of B-cell NHL is unknown.
Krober SM, Horny H-P, Greschniok A, et al [ Eberhard-Karls-Universitat, Tubingen, Germany]
Reactive and Neoplastic Lymphocytes in Human Bone Marrow: Morphological, Immunohistological, and Molecular Biological Investigations on Biopsy Specimens
J Clin Pathol 52: 521-526, 1999
The increased number of lymphocytes in a bone marrow biopsy sample could be due reactive lymphocytosis or involvement by low grade [NHL] Non Hodgkin’s Lymphoma.
This study of 529 formalin-fixed, paraffin-embeded bone marrow biopsy specimens from the iliac crest were subjected to histologic and immunohistochemical and further by PCR to determine the clonality. It was found that with increase numbers of lymphocytes over 30%, monoclonality was seen in 77% of samples.
Douglas VK, Gordon LI, Goolsby CL, et al [ Northwestern Univ., Chicago; IDEC Pharmaceuticals, San Diego, Calif]
Lymphoid Aggregates in Bone Marrow Mimic Residual Lymphoma After Rituximab Therapy for Non-Hodgkin Lymphoma
Am J Clin Pathol 112: 844-853, 1999
Rituximab, a new anti-CD20 monoclonal antibody is increasingly used in relapse low grade NHL. This study of bone marrow specimen sample following rituximab therapy was reviewed. Based solely on morphology the specimen were labelled as residual lymphoma but further immunohistochemical testing were reinterpreted as negative in many.
Remstein ED, James CD, Kurtin PJ [Mayo Clinic, Rochester, Minn]
Incidence and Subtype specificity of AP12-MALT1 Fusion Translocations in Extranodal, Nodal, and Splenic Marginal Zone Lymphomas
Am J Pathol 156: 1183-1188, 2000
In the Revised European-American Lymphoma classification [REAL] marginal zone lymphoma is divided into three categories. Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] and the provisional categories of node-based marginal zone lymphoma [MZL] and splenic MZL. This study of 99 MZL specimens subjected to reverse transcriptase -polymerase chain reaction analysed t[11;18] only in nonsplenic extranodal MZL and there by highlighting the biological differences in the MZL subgroups.
Wong K-F, Chan JK, So JCC, et al [ Queen Elizabeth Hosp, Hong Kong, China]
Mantle Cell Lymphoma in Leukemic Phase: Characterization of Its Broad Cytologic Sopectrum with Emphasis on the Importance of Distinction From Other Chronic Lymphoproliferative Disorders
Cancer 86: 850-857, 1999
Mantle Cell Lymphoma [MCL] in leukemic phase is difficult to differentiate from other chronic lymphoproliferative disorders.
This study of 14 patients in leukemic phase of MCL underwent scrutiny of cytologic features. These were recognized by irregularity and clefting seen in the nucleoli, chromatin that was moderately dense but evenly distributed, small nucleoli and scant nature of cytoplasm. The clinical course of leukemic phase of MCL was more aggressive than that seen in other lymphoproliferative disorders.
Eric P. Lester, Gina R. Petroni, Maurice Barcos, Jeffrey L. Johnson et al (Lakeland Medical Center, St. Joseph, Michigan; CALGB Biostatistical Center, Durham, North Carolina; supported by CA33601, Roswell Park Cancer Institute, Buffalo, New York; supported by CA02599, et al)
Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Etoposide (CHOPE) for Advanced-Stage Hodgkins Disease: CALGB 8856
Cancer Investigation 2001 Vol. 19 (5) Pg. 447-458
Dose intensity play a crucial role in the outcome of patients with Hodgkins disease on chemotherapy.
The standard regimens MOPP and ABVD do not have much scope for dose escalations.
This study of 92 patients of Hodgkins disease in initial cohort received IV courses of CHOPE followed by 4 courses of ABVD and the next cohort received 8 courses of CHOPE. All had advanced HD with no prior chemotherapy.
In cohort I, 92% achieved CR or PR with 4 courses of CHOPE and in cohort II, 77% achieved CR.
At conventional doses toxicity was acceptable and there is a chance of dose escalation with CHOPE. However, dose escalation is found not suitable for older patients. The possible lower toxicity profile of CHOPE especially pulmonary as compared to ABVD would make it worthwhile for this regimen with escalated doses and use of G-CSF.