Management Of non-Hodgkin Lymphoma Research Articles

Hematologic malignancies: new developments and future treatments.

An increasing number of unique active new chemotherapeutic and biologic agents are currently available for clinical research studies. Nucleoside analogs in development for non-Hodgkin's lymphoma (NHL) include clofarabine, troxacitabine, and bendamustine, a hybrid of an alkylating nitrogen mustard group and a purine-like benzimidazole, with demonstrated activity in NHL. Drugs directed at the cell cycle include flavopiridol and UCN-01. The proteasome plays a pivotal role in cellular protein regulation and activation of NFkappaB, which maintains cell viability through the transcription of inhibitors of apoptosis. PS-341 is a specific, selective inhibitor of the 26S proteasome which induces apoptosis and has activity in cell types characterized by overexpression of Bcl-2. Response rates of 50%, including complete remissions, have been reported using this agent in patients with refractory multiple myeloma. Studies are ongoing in NHL and chronic lymphocytic leukemia. G3139, an antisense oligonucleotide, has shown promise in early studies. Rituximab has revolutionized the treatment of NHL. However, other active antibodies are now available, including alemtuzumab, epratuzumab, and Hu1D10. The radioimmunoconjugates (90)Y-ibritumomab tiuxetan and (131)I-tositumomab may also play an important role in the management of NHL. Future therapeutic strategies should involve rational combinations of new chemotherapy drugs, biologic agents, and antisense compounds to increase the cure rate in patients with lymphoma.

Current trends in the management of malignant lymphoma: new WHO classification, guidelines for high-dose therapy with HSCT, and new response criteria

Several reports on the management of non-Hodgkin’s lymphoma (NHL) have recently been published, with a new classification of lymphoma being proposed. The first World Health Organization (WHO) classification of leukemia and lymphoma was published in 1976. Since that time, multiple classifications have been proposed through analyses of the immunological and clinical aspects of lymphoma. The Working Formulation (WF) for NHL was developed to resolve the classification controversies. The WF classified NHL based on clinical outcomes; however, pathologists did not agree with the disease definitions or with the terminology used. The Revised European-American Classification of Lymphoid Neoplasms (REAL classification), based on the cell of origin, was proposed subsequently. The new WHO classification adopts the REAL classification, with minor modifications and with a reassessment of the provisional categories. The first International Consensus Conference on Intensive Chemotherapy plus Hematopoietic Stem Cell Transplantation (HSCT) in Malignancies was held in 1993. At that time, the data were insufficient for a consensus to be reached. At the second conference, held in 1998, there were discussions on when and how to perform HSCT in aggressive NHL, with the task of evaluating available data. It was regarded as essential to standardize response criteria for NHL to compare recent randomized trials. The international effort to establish new response criteria was welcomed. Here, the trends and the questions that have arisen in recent developments in the management of NHL are reviewed.

Bulky centroblastic non-Hodgkin's lymphoma of the cranium vault mimicking brain involvement managed with chemotherapy. A case report

Patients with central nervous system (CNS) involvement by high grade non-Hodgkin's lymphoma (NHL) have a poor prognosis. The roles of computed tomography, radiotherapy, and intrathecal and systemic chemotherapy still need to be defined. A patient with bulky cranial lymphoma mimicking brain involvement is reported. A 62-year-old man was admitted with a huge scalp lump, headache, fatigue, and focal and generalized neurologic symptoms. Computed tomography showed an abnormal mass in the frontoparietal region involving the subcutaneous scalp, osteolytic destruction of the cranial vault, and a bulky mass that was interpreted to be intracranial. A systemic survey also revealed bulky retroperitoneal involvement and focal involvement of the spleen. Biopsy revealed a B-cell NHL of centroblastic type according to the Kiel classification. The patient was treated with a modified combination of cyclophosphamide plus mitoxantrone plus vincristine plus prednisone (CNOP) and intrathecal methotrexate. The patient responded with complete remission, including partial bone restoration of the cranium. At the time of this writing, his relapse free survival lasted 5 years. The initial interpretation of this case indicated that systemic chemotherapy with modified CNOP plus intrathecal methotrexate would be useful in the management of NHL with CNS involvement. The clinical outcome with rapid neurologic repair and also bone restoration of the cranial vault within 5 years suggests that the lymphoma probably never penetrated the dura and a successful treatment was achieved with combination chemotherapy only.

Clinical implications of cytokine and soluble receptor measurements in patients with newly‐diagnosed aggressive non‐Hodgkin's lymphoma

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Computed tomography (CT) and ultrasound (US) guided core biopsy in the management of non-Hodgkin's lymphoma

Histological examination of adequate biopsy specimens is fundamental to the management of patients with non-Hodgkin's lymphoma (NHL). A practical alternative to open biopsy, provided enough tissue can be obtained, has obvious advantages, especially if the lesion in question is deep seated, and might call for laparotomy or thoracotomy. Core biopsy with computed tomography (CT) or ultrasound (US) guidance may be such an alternative, particularly when a spring-loaded firing device is used. Thirty-four biopsies were performed in 26 patients with known or suspected NHL. A primary histological diagnosis was made in 7/7 (six NHL, one seminoma). Relapse was confirmed in 15/15 patients overall. In patients with follicular NHL, 8/15 biopsies showed progression to high grade histology. Biopsies were also performed to assess the nature of residual abnormalities after treatment and to obtain fresh tissue for immunocytochemistry. Tissue was obtained in all cases and a further procedure (two laparotomies, one second needle biopsy) was required on only three occasions. The procedure was well tolerated and there were no complications. This technique is therefore a valuable alternative to more invasive surgical procedures and may be of major benefit in the management of NHL.

Management of non-Hodgkin lymphoma in adults in Scandinavia, United Kingdom, and The Netherlands. Report from the European School of Oncology intercity meeting at Huddinge Hospital, 3rd June, 1988.

Current treatment strategies in northern Europe of non-Hodgkin lymphoma are presented. High-grade malignant lymphomas have been treated with doxorubicin-containing polychemotherapy in various modes. The advantage of six-drug regimens over CHOP-like therapy is as yet not proven. Patients with the ability to tolerate the calculated dose have good prognosis. High-dose therapy and bone marrow transplantation should be considered in poor-risk patients with lymphoblastic lymphomas in first remission, patients with all high-grade histologies in partial remission after first-line therapy and patients with relapse that are still responsive to therapy. Preliminary results from autologous bone marrow transplantation in follicular lymphoma are also encouraging. Chlorambucil induces multiple remissions in follicular lymphoma, with a median duration of the 1st, 2nd and 3rd remission being the same. The watch and wait strategy seems justified initially in most asymptomatic generalized low-grade malignant lymphomas. Systemic therapy is required in aggressive stage II-IV lymphomas. A meticulous investigation is needed for stage I patients before giving local treatment only. Immune phenotyping is of great value for diagnosis and staging. Liver, but not bone marrow involvement seems to be an adverse prognostic factor. Follicular lymphoma is an example of a dynamic tumour with gradual cellular changes associated with new and more malignant clinical signs.

Advances in management of non-Hodgkin lymphoma.

Tremendous strides have been made and newer concepts have evolved in the area of Pediatric Hematology/Oncology. In these two issues we will try to highlight these changes. Exciting developments are occurring in the area of pediatric hematology/oncology, radiation oncology and surgery to provide ideal care for children with various malignancies. Multidiscipline team approach is the key for success. The potential of cure in childhood cancer is increasing every day. Appropriate staging and institution of required therapy as early as possible needs to be done. Collaborative studies should be undertaken in India by limited number of well equipped institutions to arrive at timely conclusions from different studies. New drugs need to be screened to find effective agents and newer treatment modalities such as bone marrow transplantation need to be established in different parts of the country. The primary care pediatrician needs to be an integral part of this multidiscipline team. He needs to be well informed