Clinical Analysis Of 18 Cases With Refractory And Relapsed Diffuse Large B-Cell Lymphoma Treated With R-CHOP Regimen

Diffuse large B-cell lymphoma (DLBCL) is one of the most commonlyobserved lymphoid malignancies in adults, accounting for 30% to 40% ofnon-Hodgkin lymphoma (NHL). It develops rapidly and is prone to invade as wellas to disseminate all through the body. Many patients have been in advanced stage atdiagnosis.In 1970s, when doxorubicin was utilized with cyclophosphamide, vincristineand prednisone, forming CHOP regimen, 35% of DLBCL patients acquiredprolonged survival. Phase Ⅲ clinical trial has demonstrated that overall survivalachieved by more intensive regimens, like m-BACOD, MACOP and ProMACE-CytaBOM, is not better than CHOP. From then on, CHOP regimen has beenrecognized as the golden standard of primary treatment for DLBCL.Researchers endeavored to develop target therapy to improve outcome andreduce toxicity. Although DLBCL is one highly heterogenous disease, includingmany variants and subtypes, all of its cells express CD20 on the surface. CD20appears in pre-B cells and mature B cells, as well as B-NHL, including DLBCL, butnot in B progenitors or plasma cells. In addition, the amount of CD20 in circulationis trace, and it can't be modulated by antibody. These characteristics guaranteeCD20 become the therapeutic target of choice. Therapy for this target has been thefocus in oncology. In 1997, human mouse chimerical anti-CD20—rituximab,produced by Roche Company, was warranted as secondary treatment for indolentlymphoma. As research progresses, rituximab was found to have good effect forDLBCL. When combined with chemotherapy, rituximab can achieve excellentresult.Rituximab is the chimerical anti-CD20 monoclonal antibody formed by humanIgG1 Fc and murine Fab fragment, whose structure can achieve maximumanti-tumor effect but reduce allergy to minimum. Many anti-tumor effects werefound to be involved in the mechanism of rituximab: (1) complement-dependentcytotoxicity (CDC);(2) antibody-dependent cellular cytotoxicity (ADCC);(3) B-cellapoptosis induction;(4) inhibition of drug resistance. But it has not been decidedwhich is the predominant mechanism in vivo yet.GELA98.5 trial and prolonged research in France showed: CR rate aftertreatment of rituximab in combination with CHOP regimen (R-CHOP) was higherthan CHOP alone significantly for untreated old patients with DLBCL (agedbetween 60-80 years old), and event-free survival of the former was much higherthan CHOP alone. No significant results occurred in terms of toxicity. Mab TheraInternational Trial (MInT) mainly discussed treatment of R-CHOP for youngDLBCL patients with good prognosis, whose results demonstrated CR rate and2-year survival in R-CHOP group was obviously higher than CHOP alone, withoutsignificant difference in side effects between the two groups. As a result, NCCNconfirmed R-CHOP as new primary treatment of choice for DLBCL in 2003.After being utilized of anthracyclines as part of conventional chemotherapy, asmany as 60-65% of the patients with DLBCL could not achieve CR or relapsed afterremission. For refractory and relapsed DLBCL patients, conventional salvageregimen, like EPOCH (VP-16, prednisone, vincristine, cyclophosphamide anddoxorubicin) and ICE (ifosphamide, carboplatin and VP-16) were used frequently,but response rate was only 25-30%, with median survival of 7 months and 5-yearsurvival rate of less than 15%. Though high dose therapy/ autologous stem celltransplantation (HDT/ASCT) could increase therapeutic effect for refractory andrelapsed patients who were sensitive to chemotherapy, it has severe toxicity,especially for patients more than 60 years old. Consequently, more effectiveregimens with low toxicity are required. It is noted that rituximab alone can reachthe response rate of 30-35% for relapsed DLBCL patients and synergies withchemotherapy, so many researches have endeavored to utilize combination therapyof rituximab and chemotherapy as salvage treatment, finding response rate ofcombination therapy much higher than conventional therapy with slight side effects.This brings prospective for refractory and relapsed patients.This research analyzes 18 cases with refractory and relapsed DLBCL treatedwith R-CHOP regimen in our hospital and some other hospitals in our province from2001 to 2005 retrospectively, comparing response rate, change of LDH in serum,time to progression (TTP) and toxicity. Furthermore, we stratify all the patients andinvestigate the relationship of therapeutic effect with IPI (International PrognosticIndex) and sole lesion diameter, respectively. The following results show: responserate of R-CHOP is 83.3%, with CR rate 50.0%, much higher than response rate ofconventional salvage regimen, like EPOCH and ICE, which is 25-30%. This result issimilar with rituximab combined with ICE regimen;response rate of patients withlow IPI score is higher than that with high IPI score significantly (for patients withIPI<2, response rate is 100%,while for patients with IPI>2, response rate is 57.1%,P=0.0155). The larger the tumor lesion is, the lower the response rate is. (forpatients with sole lesion diameter <5cm, response rate is 92.9%, while for patientswith sole lesion diameter >5cm, response rate is 50.0%,P=0.0448);After treatmentof R-CHOP, the decreasing amount of serum LDH is higher than after conventionalchemotherapy obviously. (serum LDH decreases for 76.8 u/L after conventionaltherapy, while after R-CHOP, LDH decreases for 106.5 u/L averagely, P=0.00736);After treatment of R-CHOP, median TTP is 16 months, among which 10 cases ofrelapsed patients reached median TTP of 6 months after conventional chemotherapy,while after R-CHOP the median TTP is 18.5 months, P=0.04466). IPI or tumordiameter hasn't impact on TTP;Main adverse effects of R-CHOP include dyspnea,leucopenia, digestive symptoms and thrombopenia, et al in this trial, withoutsignificant difference between conventional chemotherapy. The results of thisresearch indicate: for refractory and relapsed DLBCL, response rate, decreasingamount of LDH and TTP are better than conventional chemotherapy significantly,without significant difference in toxicity between R-CHOP and conventionaltherapy.Rituximab combined with chemotherapy has achieved impressing therapeuticeffects. Besides primary therapy and salvage therapy, DLBCL treated with rituximabcombined with chemotherapy and stem cell transplantation as well as rituximabmaintenance therapy has reached inspiring results. This research demonstratedR-CHOP can be one of the most effective salvage regimens, granting one choice forclinicians.