G Digheiro, for the French Cooperative Group on Chronic Lymphocytic Leukemia (Institu Pasteur, Paris; Hopital Pitie-Salpetriere, Paris; Centre Hospitalier Regional-Hopital Sud, Ameins, Frace; et al)
Chlorambucil in Indolent Chronic Lymphocytic Leukemia.
N Engl J Med 338: 1506-1514, 1998.
The survival of patients with stage A CLL is not prolonged by treatment with chlorambucil or given intermittently with prednisone. There are advantages to deferring treatment to stage B or stage C, including postponement of the side effects of cytotoxic therapy.
Kroft SH, Domiati-Saad R, Finn WG, et al [ Univ of Texas, Dallas; Univ of Michigan, Ann Arbor]
Precursor B-Lymphoblastic Transformation of Grade I Follicle Center Lymphoma
Am J Clin Pathol 113: 411-418, 2000
This report identifies the transformation from mature follicle center B-cell to lymphoblastic lymphoma rather than from immature B-cell precursor. The evaluation of various specimen to document were Southern blot analysis for IgH, polymerase chain reaction analysis for bcl-2 gene, PCR amplification for IgH.
Nelson BP, Nalesnik MA, Bahler DW, et al [ Univ of Pittsburgh, Pa; Univ of South Alabama, Mobile]
Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Disorders: A Distinct Entity?
Am J Surg Pathol 24: 375-385, 2000
Posttransplant [ organ or bone marrow ] lymphoproliferative disorders [ PTLPDs] is associated with Epstein-Barr virus [EBV]. However, approximately 50% are EBV negative. This study of EBV-ve PTLPD reviewed the median time from transplantation to first EBV-ve PTLPD was 50 months, compared to 10 months for EBV+ve patients and these EBV-ve PTLPD were monomorphic and many succumbed in spite of chemotherapy or decrease in immunosuppression.
Copie-Bergman C, Gaulard P, Maouche-Chretien L, et al [Hopital Henri Mondor, Creteil, France; INERM U 474, Creteil, France; Hopital Laennec, Paris; et al]
The MAL Gene is Expressed in Primary Mediastinal Large B-Cell Lymphoma
Blood 94: 3567-3575, 1999
Primary mediastinal large B-cell lymphoma [PMBL] differ from peripheral diffuse large B-cell lymphoma based on clinical, morphological, and immunophenotypic characteristics.
This study by using Northern blotting and RT-PCR, could identify MAL mRNA in PMBL whereas peripheral DLBL do not express or very low levels. This gene expressed during normal T cell development is also expressed in normal thymic tissue.
Saven A, Burian C, Adusumalli J, et al (Scripps Clinic, La Jolla, Calif; Scripps Research Inst, La Jolla, Calif)
Filgrastim for Cladribine-Induced Neutropenic Fever in Patients With Hairy Cell Leukemia
Blood 93: 2471-2477, 1999
Cladribine (2 CDA) induces complete or extended remissions in patients with hairy cell leukemia.
Prolonged neutropenic fever is a common adverse effect of 2 CDA.
Filgrastim could increase the absolute neutrophil count and decrease the duration of neutropenia following 2 CDA.
Straus DJ, for the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group (Mem Sloan-Kettering Cancer Ctr, New York; et al)
Prognostic Factors in the Treatment of Human Immunodeficiency Virus-Associated Non-Hodgkin’s Lymphoma: Analysis of AIDS Clinical Trials Group Protocol 142 – Low-Dose Versus Standard-Dose m-BACOD Plus Granulocyte-Macrophage Colony-Stimulating Factor
J Clin Oncol 16: 3601-3606, 1998
The tolerance of chemotherapy in HIV associated NHL is poor and hence has reduced effectiveness.
This study of 192 patients with HIV associated NHL received standard dose m-BACOD or low dose m-BACOD plus GM-CSF as needed.
A retrospective, multivariate analysis including the following adverse risk factors such as older than 35 years, intravenous drug use, stage III/IV disease, and CD4 cell count less than 100/mL. Patients with high risk factors had poor prognosis, 3 or 4 risk factors the median survival was only 18 weeks.
These investigators had reported earlier a comparative study of low-dose v/s standard dose m-BACOD in patients with HIV associated NHL and significant difference was noted in survivals between these two, the long term survival is possible in patients with favorable risk factors.
Howarth DM, Gilchrist GS, Mullan BP, et al (Mayo Clinic Rochester, Minn)
Langerhans Cell Histiocytosis (LCH): Diagnosis, Natural History, Management, and Outcome
Cancer 85: 2278-2290, 1999
This study is a 50-year experience with LCH at Mayo Clinic. 314 patients from 2 months to 83 years were included.
96 patients had multisystemic LCH, 114 had isolated LCH, 111 of which achieved disease free survival after treatment, 44 patients had diabetes insipidus.
Patients with isolated bone LCH lesions had best prognosis and in 20% of those with multisystem involvement disease progressed despite treatment.
Wirth A, Corry J, Laidlaw C, et al (Peter MacCallum Cancer Inst, East Melbourne, Australia)
Salvage Radiotherapy for Hodgkin’s Disease Following Chemotherapy Failure
Int J Radiat Oncol Biol Phys 39: 599-607, 1997
This study of 52 patients with relapsed or refractory Hodgkin’s disease who had early received MOPP ABVD or their variants received salvage radiotherapy (SRT). The most important prognostic factor for overall survival according to multivariate analysis are presence of ‘B’ symptoms at the time of SRT, age and number of chemotherapy regimens.
The editor comments that all relapsed patients are not suitable for haematopoietic cell transplantation. Of these a small subset especially with nodal recurrence would be candidates for SRT. The total nodal irradiation following multiple chemotherapy regimens is also difficult to tolerate.
The editor states some other factors not well outlined in this study should also be considered
1) Sites of involvement at the time of relapse.
2) Bulk of disease.
3) Extranodal sites.
4) Time after chemotherapy.
5) Haematopoietic reserve.
6) Performance status.
O’Neill BP, and the North Central Cancer Treatment Group and Eastern Cooperative Oncology Group (Mayo Clinic/Found, Rochester, Minn)
Primary Central Nervous System Non-Hodgkin’s Lymphoma (PCNSL): Survival Advantages With Combined Initial Therapy? A Final Report of the North Central Cancer Treatment Group (NCCTG) Study 86-72-52
Int J Radiat Oncol Biol Phys 43: 559-563, 1999
This study of 53 patients with PCNSL received 2 courses of CHOP, external beam whole brain radiotherapy and two courses of high dose cytosine arabinoside.
The long term follow-up of this study reveals median survival of 9.6 months for the whole group and 20.7 months for the one who completed the full therapy. There was no survival difference by age or sex.
Winkler U, Jensen M, Manzke O, et al (Univ of Cologne, Germany)
Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal Antibody (Rituximab, IDEC-C2B8)
Blood 94: 2217-2224, 1999
Monoclonal antibody is reported to clear the circulating tumor cells in B-cell CLL.
This study of 11 patients who were heavily pretreated B-CLL or leukemic variant of other low grade NHL received rituximab severe first dose infusion-related toxicity was observed in patients with peripheral lymphocyte count above 50.0 X 109/L or more hence the authors recommend to reduce the circulating tumor load with chemotherapy before rituximab.
Rook AH, Wood GS, Yoo EK, et al (Univ of Pennsylvania, Philadelphia; Case Western Reserve School of Medicine, Cleveland, Ohio; Genetics Inst Inc, Cambridge, Mass; et al)
Interleukin-12 Therapy of Cutaneous T-Cell Lymphoma Induces Lesion Regression and Cytotoxic T-Cell Responses
Blood 94: 902-908, 1999
Patients with CTCL have deficiency in production of IL-12 an inducer of interferon-a production and natural killer cell cytotoxicity.
This is phase I study of recombinant IL-12 therapy in 10 patients with CTCL.
The authors could demonstrate objective response at a tolerable dose i.e. 50, 100 or 300 ng/kg subcutaneously or intralesionally twice weekly. The side effects were mild and well tolerated.
Curtis RE, Travis LB, Rowlings PA, et al (Natl Cancer Inst, Bethesda, Md; Med College of Wisconsin, Milwaukee; Fred Hutchinson Cancer Research Ctr, Seattle; et al)
Risk of Lymphoproliferative Disorders After Bone Marrow Transplantation: A Multi-institutional Study
Blood 94: 2208-2216, 1999
The posttransplant lymphoproliferative disorders (PTLD) are uncommon after allogeneic bone marrow transplantation (BMT).
This study has reviewed the records of 18,014 patients world wide who had undergone allogeneic BMT mainly for leukemia or severe aplastic anemia from HLA identical sibling (81%).
PTLD developed in 0.4% and this occurred within a year following BMT in most of the patients. The mortality in this subgroup was high. Independent predictors of risk of early onset PTLD were the use of antithymocyte globulin, T-cell depletion, mismatched related donors, acute GVHD grade II to IV or chronic GVHD or a conditioning regimen which included radiation.
Tesch H, for the German Hodgkin’s Lymphoma Study Group (Universitat Koln, Germany; et al)
Moderate Dose Escalation for Advanced Stage Hodgkin’s Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin’s Lymphoma Study Group
Blood 92: 4560-4567, 1998
The bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) is a rearranged and accelerated version of standard COPP/ABVD chemotherapy. This is an effective and safe regimen in advanced Hodgkin’s disease.
In this study 60 patients with untreated Hodgkin’s disease underwent 8 courses of chemotherapy. Areas of bulky and residual disease were irradiated. The intended doses of adriamycin, cyclophosphamide and etoposide along with G-CSF was well tolerated.
Leukocytopenia and thrombocytopenia were main toxicities. CR was possible in 93%. This moderate dose escalation of BEACOPP regimen is possible with encouraging results. However a randomized study comparing standard BEACOPP with escalated version will be more informative.
Jerusalem G, Beguin Y, Fassotte MF, et al (Univ of Liege, Belgium)
Whole-Body Positron Emission Tomography Using 18F-Fluorodeoxyglucose for Posttreatment Evaluation in Hodgkin’s Disease and Non-Hodgkin’s Lymphoma Has Higher Diagnostic and Prognostic Value Than Classical Computed Tomography Scan Imaging
Blood 94: 429-433, 1999
The activity within the residual mass following treatment of lymphoma is a common clinical dilemma for the treating oncologist.
The finding of PET with the use of 18F-Fluorodeoxyglucose (18F-FDG) has a predictive value for relapse compared with standard CT scan as disease activity is more accurately inferred by positive PET scan.
Kolb HJ, for the Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group (LM Univ, Munich)
Malignant Neoplasms in Long-term Survivors of Bone Marrow Transplantation
Ann Intern Med 131: 738-744, 1999
This study of 1036 patients from 45 European centers who underwent BMT for various reasons compared to age match control posttransplant patients had 3.8-fold higher risk of new malignant lesions.
The most common site of these were the skin, oral cavity, uterus, thyroid gland, breast and glial tissue.
The factors associated with increased risks were immunosuppression particularly with therapy such as cyclosporine or thalidomide for chronic GVHD.
Thomas FE Barth, Peter Moller, et al (Institute of Pathology, Albert-Einstein-Allee 11, University of Ulm, Germany)
Mediastinal (Thymic) Large B-Cell Lymphoma: Where Do We Stand?
The Lancet Oncology April 2002; Vol. 3(4): 229-34
This usual presentation of a young woman with cough, chest pain, dyspnoea and venous obstruction due to mass in upper anterior mediastinum and being locally invasive is now encoded 9679/3 by the new WHO classification of malignant lymphoma as mediastinal B-cell lymphoma (MBL).
The prognosis of MBL is similar to that of diffuse large B cell lymphoma as are the rates of response and remission. The lineage marker CD 20 was a clue to the B lineage. Approximately 40% of bulky tumor specimens from primary MBL tumor contains remnants of the expanded thymic epithelial network and hence MBL are assumed to be of thymic origin.
MBL express B cell lineage specific surface molecules such as CD19, CD20, CD22 and immunoglobulin associated LD79. A molecule CD30 expression in some MBL creates at times difficult diagnosis in view of similar expression in Hodgkin’s disease.
The absence of BCL-6 mutations and lack of BCL-2 and BCL-6 gene expression in MBL distinguish it from other DLCL at molecular level.
The highly characteristic profile of genetic aberration is involvement of chromosome 9 and chromosome X provide strong evidence for the existence of a specific sequence of genetic events during the neoplastic transformation of MBL.
The treatment of MBL and its initial response was an important predictor of outcome. In one of the study, time intensive chemotherapy regimens such as MACOPB followed by consolidation, radiotherapy a 86% complete remission and 93% progression free at 96 month was possible.
However the use of high dose chemotherapy followed by autologous hemotopoietic stem cell transplantation also support the hypothesis that MBL may be more responsive to time intensive therapies than other DLCL. At present no recommendation can be made for treatment strategies.