Prognostic value of serum beta-2 microglobulin in low-grade lymphoma

OBJECTIVE: To evaluate serum beta-2 microglobulin (beta-2M) and other prognostic indicators in previously untreated low-grade lymphoma. DESIGN: Cohort study of 80 patients with uniformly treated low-grade lymphoma, followed for a median of 21 months. These 80 patients, all of whom had serum beta-2M drawn within 2 weeks before starting therapy, were derived from a cohort of 119 previously untreated patients entered into one of three clinical trials. SETTING: Tertiary referral cancer center. PATIENTS: Eighty previously untreated stage I to IV patients (mean age, 55 years). INTERVENTION: Treatment was given according to Ann Arbor stage: Patients in stage IV were treated with CHOP-bleomycin and maintained on interferon therapy; those in stage III received CHOP-bleomycin and radiotherapy; and those in stages I and II received COP-bleomycin and radiotherapy. MEASUREMENTS: Outcome was determined by assessing complete remission rate and time to treatment failure. Univariate and multivariate analyses were used. RESULTS: The complete remission rate for patients with a beta-2M level of 3.0 mg/L or greater was 36% compared with 71% for those with a level of less than 3.0 mg/L. Using multivariate analysis that tested beta-2M as a continuous variable, it was selected as the most significant factor for complete response. The adjusted odds ratio was 0.285 (95% CI, 0.101 to 0.809). The Ann Arbor stage had marginal significance (adjusted odds ratio, 0.435; CI, 0.150 to 1.263). For time to treatment failure, beta-2M was the only variable retained in the multivariate model. At 42 months, no patient with a beta-2M level of 3.0 mg/L or greater was projected to be in remission as compared with 85% of patients with a beta-2M level of less than 3.0 mg/L. CONCLUSIONS: The serum beta-2M level is a good predictor of complete response and time to treatment failure. A larger number of patients should be studied to clarify the role of other potentially independent variables such as stage and age.     

New prognostic model for extranodal natural killer/T cell lymphoma,nasal type

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p?<?0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p?<?0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.     

Significance of circulating Epstein-Barr virus DNA monitoring after remission in patients with extranodal natural killer T cell lymphoma

Circulating Epstein-Barr virus (EBV)-DNA has been established as a useful parameter for diagnosis and predicting prognosis in patients with extranodal natural killer T cell lymphoma (ENKTL); however, the role of monitoring of circulating EBV-DNA after complete remission (CR) is not well established. From January 2008 to August 2016, 328 ENKTL patents were enrolled in 2 lymphoma cohorts. Of 171 patients achieved a CR, 81 had available monitoring data for circulating EBV-DNA with negative post-treatment EBV-DNA. Measurement of circulating EBV-DNA was performed from unfractionated whole blood and calculated according to WHO international standards. Median duration of follow-up was 40.4 months. In 31 of the 81 patients (38.8%), circulating EBV-DNA was detected at least once during follow-up, and 16 of these patients (51.6%) experienced relapse. In contrast, only 7 out of 50 (14.0%) patients with consistently undetectable circulating EBV-DNA experienced relapse (p?<?0.001). In multivariate analysis, positive conversion of circulating EBV-DNA was the only independent prognostic factor for occurrence of relapse (HR?=?6.552, p?<?0.001), progression-free survival (HR?=?4.549, p?=?0.01), and overall survival (HR?=?8.726, p?<?0.001). Patients with a higher level of circulating EBV-DNA than 3310 IU/mL (3.52 log₁₀ IU/mL) showed a strong tendency to relapse (73.3 vs. 31.3%, p?=?0.019). In conclusion, positive conversion of circulating EBV-DNA was a valuable indicator of relapse and inferior survival, especially if the level was higher than 3310 IU/mL in ENKTL patients had achieved CR. Close follow-up is necessary for patients developed detectable circulating EBV-DNA after remission.     

Esophageal actinomycosis after allogeneic peripheral blood stem cell transplantation for extranodal natural killer/T cell lymphoma,nasal type

We report a 19-year-old man with extranodal natural killer (NK)/T cell lymphoma, nasal type treated by allogeneic peripheral blood stem cell transplantation (allo-PBSCT). His lymphoma was chemoresistant, and disseminated during local radiotherapy. The patient received allo-PBSCT from his HLA-1 locus mismatched sister using busulfan (BU), cyclophosphamide (CY) and VP-16 as the conditioning regimen. His course was complicated by esophageal actinomycosis 9 months after transplantation, which resulted in the rupture of the right common carotid artery. These observations suggest that actinomycosis should be monitored carefully after transplantation in patients who have received local radiation therapy before the procedure.     

Regression of the tumor after withdrawal of cyclosporine in relapsed extranodal natural killer/T cell lymphoma following allogeneic hematopoietic stem cell transplantation

The prognosis of patients with advanced-stage extranodal natural killer/T cell lymphoma, nasal type (ENKL) has been generally poor, and several anecdotal reports have suggested the role of allogeneic hematopoietic stem cell transplantation (HSCT). A potential advantage of allogeneic HSCT may be the graft-versus-lymphoma (GVL) effect. The susceptibility to the GVL effect, however, has been shown to vary according to histologic subtypes, and it has been hardly documented yet whether ENKL is susceptible to the GVL effect. Here we report a patient with advanced-stage ENKL who underwent allogeneic HSCT from an HLA one-allele mismatched related donor, whose clinical course after HSCT suggested the potent GVL effect against ENKL. A 43-year-old female underwent allogeneic HSCT for advanced-stage, chemorefractory ENKL, and achieved complete response. In 4 months after the transplantation, however, the ENKL relapsed in multiple sites. These lesions markedly responded to the discontinuation of immunosuppressive agents and disappeared. Except for a temporal exacerbation of bronchiolitis obliterans organizing pneumonia, she has been free from disease for more than a year without other treatments against lymphoma. The clinical course of the current patient suggests the potent GVL effect against ENKL. Allogeneic HSCT, including that with reduced-intensity regimens, is a promising treatment option for high-risk ENKL.     

Pulmonary extranodal natural killer/T-cell lymphoma: clinical analysis of three cases

<正>Objective To improve the understanding of pulmonary involvement of extranodal natural killer/T-cell lymphoma (ENKTL) by analyzing the clinical manifestations,imaging and pathological features of this disease.Methods Three cases of ENKTL,proven by pathological diagnosis in Fuzhou General Clinical Medical College of     

Aggressive natural killer cell leukaemia/lymphoma in two patients with lethal midline granuloma

Summary. We report two patients with leukaemic proliferations of large granular lymphocytes. The immunophenotype study showed that the leukaemic cells were positive for CD2, CD38, CD56 and anti-HLA-DR monoclonal antibodies and negative for other T-cell (CD3, CD4, CD8) and B-cell markers (CD19, CD20 and surface immunoglobulins). The clinical course was acute and a diagnosis of aggressive natural killer cell leukaemia/lymphoma was made. No clonal rearrangements of either Cβ T-cell receptor or J_H immunoglobulin genes were found. Functional studies done in one patient demonstrated non-restricted cytotoxic activity after activation with IL-2. Lethal midline granuloma had been previously diagnosed in both patients. A possible relationship between this entity and the natural killer cell leukaemia is discussed.     

Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma,nasal type

Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50–56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2–6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.     

Prognostic factors for classifying extranodal NK/T cell lymphoma, nasal type, as lymphoid neoplasia

This study evaluated the applicability of prognostic factors commonly used for diagnosis of classical lymphoma outcomes to extranodal NK/T cell lymphoma, nasal type (NTCL). Clinical features and their associations with lactate dehydrogenase (LDH) were evaluated in 70 patients. RLDH was defined as the ratio of LDH to the upper normal limit. RLDH was associated with stage (I-II vs. III-IV), lymph node involvement (LNI), and International Prognostic Index score (<2 vs. > or =2). Poor performance status and advanced stage were common in patients with local tumor invasiveness (LTI). LDH level, classified into three levels (low, high, and very high) was associated with survival (P < 0.001). In multivariate analysis, the predictive values of LDH level, B symptom, performance status, and stage remained significant whereas those of LTI and LNI did not. Scoring was performed by weighting each factor with 0.5 or 1.0 according to its hazard ratio. Scores were classified into four groups. Groups with high scores were associated with unfavorable outcomes (P < 0.001). Current study suggests that prognostic factors for NHL may be useful to predict the outcome of NTCL but the model should take LDH level and the prognostic weight of each factor into account.     

The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T‐cell lymphoma,nasal type

The Glasgow Prognostic Score (GPS), an inflammation‐based prognostic score including C‐reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T‐cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T‐cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression‐free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low‐risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. Am. J. Hematol. 88:394–399, 2013. © 2013 Wiley Periodicals, Inc.     

Angiocentric nasal T/natural killer cell lymphoma: a single centre study of prognostic factors in 108 patients

Angiocentric T cell/natural killer (NK) nasal lymphoma remains a rare clinical presentation in North America and Europe but is more common in Asia and Latin America. We have reviewed 108 cases of angiocentric T/NK cell lymphoma of the nasal cavity with a view to establishing prognostic factors. Most patients were high or high intermediate clinical risk and had additional poor prognostic factors such as bulky disease, high levels of beta 2 microglobulin, advanced stage and multiple extranodal involvement. At 8 years, overall survival was 82%, 90% and 84% for low-intermediate, high-intermediate and high clinical, respectively. Disease free survival was very similar: 79%, 83% and 80%, respectively. Multivariate analysis did not identify any factor influencing overall survival and disease-free survival. There was no evidence that the international prognostic index (IPI) was applicable in these patients and it appears that angiocentric T/NK cell lymphoma is an independent prognostic factor itself.