PHASE II STUDYCOMPARING TREATMENT WITH R-DHAP VERSUS DHAP IN RELAPSED & REFRACTORY AGGRESSIVE DIFFUSE LARGE B-CELL LYMPHOMA

Abstract

Non-Hodgkin’s lymphomas (NHL) representa large group oflympho-proliferative disorders which originate in B-lymphocytes, T-lymphocytes or natural killer (NK) cells (Shankland et al., 2012). Non-Hodgkin Lymphoma risk is associated with a number of risk factors. Many risk factors have enough or convincing evidence of increased risk of lymphoma such as working in rubber manufacture, Epstein-Barr virus (EBV), immune suppression related hepatitis C virus (HCV) , human immunodeficiency virus (HIV) type I, human T-cell lymphotropic virus type 1 (HTLV-1), kaposi sarcoma herpes virus (KSHV), helicobacter pylori (H. Pylori), azathioprine, and cyclosporine (Cogliano et al., 2011). The most frequent clinical entities recognized by the REAL/WHO classification are diffuse large B-cell lymphoma (31%), follicular lymphoma (22%), lymphoma of MALT type (8%), small lymphocytic lymphoma (7%), mantle cell lymphoma (6%), peripheral T-cell lymphoma (7%), primary mediastinal large B-cell lymphoma (2%), anaplastic large T /null-cell lymphoma (2%), lymphoblastic lymphoma of T- or B-cell lineage, marginal zone (monocytoid) B-cell lymphoma (2%), lymphoplasmacytic lymphoma (2%), Burkitt’s lymphoma (2%), and other (9%) (Evens et al., 2015). Diffuse large B-cell lymphoma is the most common type of NHL nearly 30% of all lymphoid malignancies. It is associated with an aggressive natural history, with a median survival of less than one year in untreated patients (Flowers et al, 2010). Although DLBCL occurs in a broad age range, the median age is in the sixth decade. A rapidly enlarging lymph node is a frequent presenting feature, but in up to 40% of patients, the site is extra-nodal. Mostly 30% of patients present with stage IV disease, about a third have B symptoms, and more than half have an elevated serum lactate dehydrogenase (LDH).And about 15% of patients have involved bone marrow. Diffuse large B-cell lymphomas may involve privileged sites, such as the testis and CNS. CNS involvement has a poor prognosis(Rana et al., 2014). To diagnose it needs to examine morphology, immunohistochemistry,andflowcytometry by an experiencedlymphomapathologist and, where appropriate, molecular studies to accurately categorize the lymphoma A fine-needle aspirate is not enough forinitial diagnosis. It is preferred to takean incisional or excisional biopsy toprovide adequate tissue for these examinations, if it is not possible or it is essential to document relapse, a core-needlebiopsy can be considered; but, if it is a nondiagnostic sample it must befollowed by an incisional or excisional biopsy. With consent, additionalparaffin-embedded, fresh-frozen tissue, or cell suspensionsshould be stored for future research (Cheson et al., 2014). To evaluate the patient clinically, it is essential to take a comprehensive history includingage; sex; absence/presence of fevers to more than 101°F (38.3°C),chills, drenching night sweats, or unexplained weight loss more than10% of body mass over 6 months; and history of malignancy. Fatigue,pruritus, and alcohol-induced pain in patients withHLshould also benoted. While these factors rarely change treatment plan, their recurrence may herald disease relapse (Zucca et al., 2013). During physical examination, you should measure accessible nodalgroups and the size of the spleen and liver in centimeters below theirrespective costal margins in the mid-clavicular line. But, the sensitivityof physical examination changes among observers. Therefore, CT imaging is essential to formally define organomegally (chesonet al., 2014). For fluorodeoxyglucose(FDG) -avid NHL subtypes, PET and PET-CT increase the accuracyof staging in comparison with CT scans for nodal and extra-nodal sites. PET-CT changes stage in almost one third ofpatients,moreoftenupstaging, although alteration in management occurs in fewer patients,with no demonstrated impact on overall outcome. Now, fewer patients are undertreated or overtreated due to improving staging accuracy (Cheson et al., 2011). Prognostic Index (IPI) score, which was proposed in 1993 to assign prognosis to patients with aggressive non-Hodgkin lymphoma undergoing treatment with doxorubicin-containing chemotherapeutic regimens. These findings have been confirmed in many series of patients with DLBCL (Freedman et al., 2014). The sIPI, evaluatedbeforestarting chemotherapy, includes 5 risk factors: age older than 60 years, extranodal sites more than 1, LDH more than upper limit of normal, stage III or IV disease, and Karnofsky performance status (KPS) less than 80% or WHO-PS greater than 1. The sAAIPI, evaluatedbeforestarting chemotherapy, includes 3 of the IPI risk factors: LDH, stage, and KPS or WHO-PS. These factors are similar to the age-adjusted prognostic index described by Shipp et al in patients with de novo diffuse large cell lymphoma. sAAIPI groups are low risk (L) with zero factors, low-i