Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report
M.D. Luigi Pisani - Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report
Summary
The author presents the case of a patient with large B-cells non-Hodgkin's lymphoma in clinical stage IV-A (in the absence of systemic symptoms)-E (extranodal sites were the skin, kidneys, and likely the right breast)-X (for the considerable size of the thoracic skin lesion), with high prognostic index according to the IPI, International Prognostic Index ("A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project", see below), for which she was given an aggressive chemotherapy program.
The therapeutic program included 8 cycles of chemotherapy according to the MACOP-B scheme consists of the following drugs:
- Methotrexate (Brand names Rheumatrex Dose Pack, Trexall, Methotrexate and so on - Side effects);
- ARA-C, it is also known as Arabinofuranosyl Cytidine or Cytarabine or Cytosine Arabinoside (Brand names Cytosar-U, Tarabine PFS, Cytosar and Depocyt - Side effects);
- Cyclophosphamide (Trade/Brand names Procytox, Neosar, Cyclophosphane, Cytophosphan, Cyclostin, Sendoxan, Clafen, Endoxan and so on - Side effects);
- Vincristine (Brand name Oncovin and Vincasar PFS - Side effects);
- Prednisone (Brand names Cortan, Deltasone, Prednisolone and so on - Side effects);
- Bleomycin (Brand name Blenoxane or generic only - Side effects);
at the end of which, on the basis of the results obtained, it was decided the subsequent therapeutic strategy.
The treatment was suspended for the occurrence of severe toxicity because of which the patient decided to undertake a course of treatment according to the DBM (The Di Bella Method). The clinical picture that came to my observation was as follows:
Introduction
NHLs are a heterogeneous group of malignant lymphoproliferative disorders with different clinical behaviors and biological origins.
The etiology of most NHL continues to be poorly understood and their incidence increases exponentially with age. The NHL may occur preferentially affecting different anatomical sites, they debut involving more lymph nodes and extend to the spleen, bone marrow and to the other tissues and organs.
Primitives extralymphatic locations are found in 20-30% of cases and preferentially affecting the gastrointestinal tract, the skin, the central nervous system and testicles.
With regards to the etiology a number of risk factors have been associated with the onset of the NHL, including: genetic factors, infections, congenital and acquired immunodeficiency conditions, physical and chemical agents.
The classification of NHL has been changed several times during the last four decades and this has been a source of confusion and frustration for physicians. Currently they are classified according to a system called REAL (Revised Eureopean American Lymphoma: publication "A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group", see below) that is assigned on the basis of their derivation from B lymphocytes, T or NK.
After making a diagnosis of NHL, you must perform several tests to identify all sites of disease and determining the prognosis based on known clinical risk factors. The staging has become more accurate and more complicated with the advent of non-invasive tests and the availability of more sophisticated means such as Positron Emission Tomography (PET).
The Ann Arbor staging system (see below), originally designed to determine the anatomical spread of the Hodgkin's disease, remains the most widely used staging system for NHL, despite its incompleteness.
In this particular case it is a large B-cell lymphoma (diffuse large cell lymphoma, DLCL), which represents 40% of all lymphomas and is characterized by the presence of large phenotype B cells with cleaved nucleus or multi lobed, clearly evident nucleolus and basophilic cytoplasm.
The disease begins with both lymph node and extranodal masses rapidly growing. Often the lymph node masses have "bulky" features, especially in the mediastinum and abdomen. The NHL like the other hematopoietic malignancies, should be considered systemic diseases.
Those primitive of the gastrointestinal tract, of the Skin, Testis and in particular of the Central Nervous System tend to remain confined to the tissue of origin even in the advanced stages of the disease.
The treatment aims to the cure of the widespread and aggressive lymphomas since for these groups of malignancies is now possible to obtain a high percentage of durable complete remissions using modern schemes of intensive polychemotherapy, including high-dose treatment with support of circulating hematopoietic precursors.
In lymphomas of indolent manifestation does not seem currently possible to obtain a healing with the therapeutic means available today, probably due to one of the oncogenes of the drug resistance (bcl-2), accordingly the treatment aims primarily to a long control of the disease by using little aggressive therapies.
Method
In view of the unsatisfactory activity demonstrated by systemic chemotherapy, I decided to build in a patient treatment with Octreotide, All-trans retinoic acid, Melatonin, Cyclophosphamide, Cabergoline, Codex V soothing paste and Codex V10 Oleogel.
The aim of the treatment is to inhibit angiogenesis by exploiting the potential of the somatostatin analogs and the administration of octreotide was corroborated by the fact that several tests had confirmed that somatostatin analogs have antiproliferative action in experimental tumors, although it is not yet fully clear the mechanism by which they exert their effect.
The inhibition of tumor growth may be due to different mechanisms:
- Inhibition of angiogenesis and stimulation of apoptosis;
- Blood flow reduction in the tumor;
- Direct antiproliferative effect by binding with the receptor;
- Indirect antiproliferative effect by inhibiting the release of growth factors (IGF-1);
- Inhibition of hormones such as insulin, GH, gastrin, CCK, secretin which regulate tumor growth;
- Modulation of the immunological activity;
- Antimitotic direct effects.
The topical application of Codex V soothing paste and Codex V10 Oleogel, products containing substances with trophic, keratoplastic action and activator of the immune response was deemed necessary to take advantage of these properties, that is to rebalance and to reactivate the immune response in the lymph nodes and especially to take advantage of their powerful and soothing action and at the same time of the effective reactivation of tissue trophism as well.
Outcome
For 36 months the patient underwent the therapeutic treatment described above, in combination with other drugs that have been modulated over time in relation to follow-ups, recommended by the guidelines, periodically carried out.
The examination significantly highlights the disappearance of the skin lesions, as documented by the images, in the absence of side effects and drug toxicity. In the following images it is possible to highlight the progressive evolution of the regression of the lesion:
Situation after 20 months - Nov/2003
Situation after 27 months - 06/Jun/2004
Situation after 32 months - 01/Nov/2004
Situation after 36 months
Conclusions
The obtained result, considering the absence of side effects, appears to be very promising and worthy of further studies.
I therefore believe that the therapy with therapeutic protocol according to the DBM (The Di Bella Method) may represent a valid alternative to the treatments currently used, especially with regard to the fact that the antineoplastic chemotherapeutic agents, drugs with narrow therapeutic index, whose toxicity, attributable to to the inability to discriminate between normal cells and cancer cells, determine consequences related to their use; in fact, they are responsible, on the one hand, for the occurring of adverse events, even severe, with a worsening of the quality of life of patients and, on the other hand, of a reduced tumor control and above all because the occurrence of toxicity limits the dosage and therefore it is not possible to achieve the effective therapeutic dose.
Bibliography
- Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, et al. - A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361-92;
- Oomen SP, Hofland LJ, van Hagen PM, Lamberts SW, Touw IP. - Somatostatin receptors in the haematopoietic system. Eur J Endocrinol. 2000 Oct;143 Suppl 1:S9-14;
- Pollak MN, Schally AV. - Mechanisms of antineoplastic action of somatostatin analogs. Proc Soc Exp Biol Med. 1998 Feb;217(2):143-52;
- Reubi JC, Schaer JC, Markwalder R, Waser B, Horisberger U, Laissue J. - Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance. Yale J Biol Med. 1997 Sep-Dec;70(5-6):471-9;
- Maloney DG. - Non-Hodgkin's lymphoma. Curr Opin Hematol. 1995 Jul;2(4):255-61;
- Schally AV. - Oncological applications of somatostatin analogues. Cancer Res. 1988 Dec 15;48(24 Pt 1):6977-85;
- Longo DL. - Non-Hodgkin's lymphoma. Curr Opin Hematol. 1994 Jul;1(4):295-302;
- Weckbecker G, Raulf F, Stolz B, Bruns C. - Somatostatin analogs for diagnosis and treatment of cancer. Pharmacol Ther. 1993 Nov;60(2):245-64;
- Woltering EA, Watson JC, Alperin-Lea RC, Sharma C, Keenan E, Kurozawa D, Barrie R. - Somatostatin analogs: angiogenesis inhibitors with novel mechanisms of action. Invest New Drugs. 1997;15(1):77-86;
- Skarin AT1, Dorfman DM. - Non-Hodgkin's lymphomas: current classification and management. CA Cancer J Clin. 1997 Nov-Dec;47(6):351-72 (see below):
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