Management Of Hematologic Malignancies Research Articles

Use of Interleukin-2 in the Management of Haematological Malignancies

Interleukin (IL)-2 is a glycoprotein lymphokine which induces proliferation of all subclasses of T-lymphocytes, natural killer cells and lymphokine activated killer cells, differentiation of cytotoxic cells and secretion of other cytokines, especially interferon-gamma. A fundamental property of IL-2 activated effector cells is to selectively lyse freshly isolated tumour cells. Work carried out on animal tumour models and application in human therapeutics has suggested the potential value of an immunotherapeutic approach in haematological malignancies, especially in the setting of minimal residual disease. Extensive phase I/II trials have been conducted in all haematological diseases, but the most interesting results have been obtained in acute myeloid leukaemia and non-Hodgkin's lymphoma, where the possibility of achieving partial and complete responses in patients with advanced disease has been reported. The feasibility and immunomodulatory effects of IL-2 treatment in patients with minimal residual disease after high-dose chemotherapy have also been explored. However, the heterogeneity of cases treated and administration schedules used does not allow definitive conclusions to be drawn about the true impact of IL-2 treatment on the prognosis of these patients. The clearly encouraging results reported in the literature deserve further investigation from a biological and clinical point of view; until the role of IL-2 in haematological malignancies has been identified, it should be used only in the investigative setting of clinical trials.

Colonic Adenomas with Extramedullary Myeloid Tumor (Granulocytic Sarcoma)

Extramedullary myeloid tumor (EMT) is an accumulation of malignant immature cells of the granulocytic series that is usually green in appearance due to the presence of myeloperoxi-dase. These invasive and destructive tumors occur most commonly in the skull and surrounding tissues, lymph nodes, skin and soft tissues. Regardless of the site, EMTs are difficult to recognize and may be easily overlooked or diagnosed as malignant lymphoma. EMTs may precede the diagnosis of a chronic myeloproliferative disorder or acute myeloid leukemia, may present coincident with the hematologic diagnosis, or may herald a relapse after therapy. An accurate diagnosis of EMT is of great clinical importance in the ongoing management of hematologic malignancies. We report here two unusual cases of EMT of the colon, which infiltrated adenomatous polyps. We conclude that increased cellularity within the lamina pro-pria of polyps and mucosal surfaces in general should be carefully examined.

Modern molecular diagnostics and the management of haematological malignancies.

The advent of molecular biological techniques has led to a radical improvement in the evaluation of haematological disorders and offers exciting future prospects. In particular it has led to the improved recognition of distinct clinicopathological entities defined by a combination of morphological, immunophenotypic and chromosomal features. Antibody-based techniques, namely immunophenotyping and immunocytochemical techniques, are essential to malignant haematological diagnosis. More novel is the diagnostic use of antibodies against novel fusion proteins, for example in AML, M3 and anaplastic lymphoma. PCR-based techniques allow the identification of genetic mutations and translocations including such common translocations as t(14;18), t(9;22), inv 16 and t(8;21). Fish-based techniques are greatly improving the ability to detect genetic abnormalities including those conditions with low cell proliferation and current research-based techniques include the combination of FISH with cell surface markers (FICTION), FIBRE FISH and Comparative Genomic Hybridization. Molecular techniques are essential in monitoring residual disease which is best illustrated in CML. The development of real-time automated PCR offers exciting prospects in this field. The increasing number of tests, the need for an integrated approach to diagnosis and the need for cost effectiveness indicate that such services should be provided by a specialized haematology laboratory.

Therapeutic management of hematological malignancies in elderly patients. Biological and clinical considerations. Part III: The chronic leukemias and myelofibrosis.

The different therapeutic options available for the treatment of chronic leukemias and myelofibrosis are discussed. In reference to chronic myeloid leukemia (CML), the choice of the most appropriate treatment must take into account not only the clinical condition but also the age of the patient. While subjects under 50 might benefit from the options offered by alpha-interferon, bone marrow and peripheral stem cell transplant, in older age groups treatment of the chronic phase must still rely on standard treatment. Chronic lymphocytic leukemia (CLL) and its variants is a disease of mostly middle and late life, with a variable clinical course. Patients show wide differences in morbidity and mortality. Many features have been shown to influence the prognosis, and the most important ones are incorporated into the staging systems currently in use. The results obtained from the study of large trials support the concept that treatment of patients with stable stage A CLL should be postponed until progression of disease. Treatment relies principally on alkylating agents, corticosteroids and radiation therapy; the new nucleoside analogues, such as fludarabine and 2-chlorodeoxyadenosine, have recently acquired established value in improving overall survival. With regard to myelofibrosis, the histological and biological features that influence the natural course of the disease are described, as well as the choice of the most appropriate treatment, which ranges from the use of alkylating agents and androgens, to splenectomy and splenic irradiation.

Therapeutic management of hematological malignancies in elderly patients. Biological and clinical considerations. Part II: Non-Hodgkin lymphomas and Hodgkin's disease.

Increased knowledge of the nature and biology of lymphoid cells has provided more rational classification schemes, and has improved therapeutic strategies. However, non-Hodgkin lymphomas (NHL) as well as Hodgkin's disease (HD) show a less favorable outcome in elderly compared to young patients. The poorer outcome in elderly patients with NHL is largely due to chemotherapy-related issues, although other age-related factors may contribute to determine a poor prognosis, such as the presence of more aggressive pathological subtypes and an increase in extranodal vs nodal presentations. Similarly, HD patients older than 50 years have higher rates of advanced disease, B symptoms, and histological types associated with poor prognosis at presentation. The poor prognosis in lymphoid malignancies also appears to be attributable to inadequate treatment. However, the inability to administer full therapy may be real, due to the high percentages of deaths caused by severe infections and intercurrent disease (cardiac, renal, lung) related to diminished organ function. The availability of growth factors may help to reduce the incidence of severe neutropenia and other related septic conditions.

Therapeutic management of hematological malignancies in elderly patients. Biological and clinical considerations. Part 1. Myelodysplasias and the acute leukemias.

The different therapeutic options that may be employed in the treatment of elderly patients with acute leukemias and myelodysplastic states are considered following an analysis of certain biological features, that have been investigated by cytochemical, cytogenetic and cytokinetic techniques, immunophenotyping, and studies on G-6-PD isoenzymes. These studies imply that in the elderly the pattern of hematological malignancies and the lack of response to conventional treatment derive from intrinsic biological differences between these pathological states in older and younger patients. Treatment in elderly patients has ranged from palliative treatment to intensive chemotherapy, often with disappointing results in both cases. Palliative treatment does not induce remissions, and median survival is short. On the other hand, elderly patients do not tolerate well both induction and post-remission therapy due to the degree of toxicity and the effects of drug-induced pancytopenia. In this scenario, in vitro drug-sensitivity testing and karyotyping assume increasing importance, because they may predict which patients are likely to benefit from intensive therapy. In both acute leukemias and myelodysplasias, treatment ideally should be designed case by case, according to the hematological, clinical and biological features.

Purine nucleoside analogues: fludarabine, pentostatin, and cladribine

Purpose. The primary objective of this article is to continue the discussion of the pharmacology, phar macokinetics, clinical use, and adverse effects of the currently approved adenosine analogues, focusing on pentostatin. This is part two of a three part series. Data Sources. We reviewed the literature through a MEDLINE search from 1986 to 1996. Rele vant articles cited in the literature obtained by MED LINE searching also were considered. We searched the following terms: fludarabine, cladribine, pentosta tin, apoptosis, and adenosine analogues. The search was restricted to the English language. Data Extraction. We have reviewed the current literature in regard to the chemistry, mechanisms of action and pharmacology, pharmacokinetics, clinical use, adverse effects, drug interactions, indications, formulation, dosage, administration, and pharmaceu tical issues of the currently approved adenosoine analogues, focusing on pentostatin. Data Synthesis. The adenosine analogues are structurally similar agents used in the management of hematological malignancies. Pentostatin and cladrib ine are both active agents in the treatment of hairy cell leukemia. There are no comparative clinical trials between the agents, and we have provided compari sons based on pharmacology, clinical experience, adverse effects, and cost.

Review : Purine nucleoside analogues: Fludarabine, pentostatin, and cladribine

Purpose. An introductory template for an extensive discussion of the pharmacology, pharmacokinetics, clinical use and adverse effects of the currently ap proved adenosine analogues: fludarabine, pentostatin, and cladribine is profiled. This is part one of a three-part series. Data Sources. We reviewed the literature through a MEDLINE search from 1986 to 1996. Relevant articles cited in literature obtained by MEDLINE searching were also considered. We searched the following terms: fludarabine, cladribine, pentostatin, apoptosis and adenosine ana logues. The search was restricted to the English language. We have incorporated pricing information from our prac tice sites as well as the average wholesale price for the purpose of cost comparison. Data Extraction. We have reviewed the current literature with regard to the chemistry, mechanisms of action and pharmacology, pharmacokinetics, clinical use, adverse effects, drug interactions, indications, formulation, dosage, administration, pharmaceutical issues and a cost comparison of the currently approved adenosine ana logues, fludarabine, pentostatin, and cladribine. Data Synthesis. The adenosine analogues are struc turally similar agents used in the management of hemato logical malignancies. Fludarabine and cladribine exhibit significant activity in CLL (chronic lymphocytic leukemia) and NHL (non-Hodgkin's lymphoma) and pentostatin and cladribine are both active in the treatment of hairy cell leukemia. There are no comparative clinical trials between the agents and we have provided comparisons based on pharmacology, clinical experience, adverse effects and cost as well as reviewing the clinical use of these agents. Conclusion. The adenosine analogues, fludarabine, pentostatin, and cladribine, represent an important ad vance in the treatment of indolent lymphoid malignancies. Although response rates for fludarabine and cladribine in chronic lymphocytic leukemia and for pentostatin and cladribine in hairy cell leuemia are improved over standard therapy, the true clinical impact of these agents has not yet been realized. Additional studies in larger populations of both previously treated and untreated patients, as well as comparative trials between the deoxyadenosine analogues themselves need to be carried out. Moreover, combination chemotherapy trials with deoxyadenosine analogues and other cytotoxic agents need to be performed to determine the efficacy and toxicity of these combinations in various lymphoid malignancies.

Interleukin 2 in the management of hematologic malignancies

Interleukin 2 in the management of hematologic malignancies