Speciality
Spotlight

 




 


Oncology


 

 





Lymphoma

 

  • 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-Hodgkin’s Lymphoma

    J
    Clin Oncol 16: 41-47, 1998


     

    Interferon
    a
    is known to have significant activity in patients with
    low-grade malignant non-Hodgkin’s 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 IFN
    a-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 d’Etude des Lympphomes
    Folliculaires, Caen, France; Groupe d’Etude 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 d’Etude 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 d’Etude
    des Lymphomes Folliculaires, Caen, France; Groupe
    d’Etude des Lymphomes Folliculaires, Creteil, France;
    Groupe d’Etude 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 d’Etude 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 Hodgkin’s
    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 Hodgkin’s Disease [Univ of Leipzig, Germany;
    et al]

    A Prognostic
    Score for Advanced Hodgkin’s 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 Hodgkin’s 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 Hodgkin’s 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 Hodgkin’s 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 Rituximab’s 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-Hodgkin’s
    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 – Hodgkin’s
    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-Hodgkin’s 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 Hodgkin’s Disease: CALGB 8856 

    Cancer Investigation 2001 Vol. 19 (5) Pg. 447-458

           

    Dose intensity play a crucial role in the outcome of patients with Hodgkin’s disease on chemotherapy.

           

    The standard regimens MOPP and ABVD do not have much scope for dose escalations.

          

    This study of 92 patients of Hodgkin’s 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.

         


 

 



 

 

Speciality Spotlight

 

 

Lymphoma
 

  • 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-Hodgkin’s Lymphoma
    J Clin Oncol 16: 41-47, 1998
     
    Interferon a is known to have significant activity in patients with low-grade malignant non-Hodgkin’s 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 d’Etude des Lympphomes Folliculaires, Caen, France; Groupe d’Etude 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 d’Etude 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 d’Etude des Lymphomes Folliculaires, Caen, France; Groupe d’Etude des Lymphomes Folliculaires, Creteil, France; Groupe d’Etude 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 d’Etude 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 Hodgkin’s 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 Hodgkin’s Disease [Univ of Leipzig, Germany; et al]
    A Prognostic Score for Advanced Hodgkin’s 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 Hodgkin’s 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 Hodgkin’s 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 Hodgkin’s 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 Rituximab’s 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-Hodgkin’s 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 – Hodgkin’s 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-Hodgkin’s 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 Hodgkin’s Disease: CALGB 8856 
    Cancer Investigation 2001 Vol. 19 (5) Pg. 447-458
           
    Dose intensity play a crucial role in the outcome of patients with Hodgkin’s disease on chemotherapy.
           
    The standard regimens MOPP and ABVD do not have much scope for dose escalations.
          
    This study of 92 patients of Hodgkin’s 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.
         

 

 

 

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