scholarly journals Autologous Stem Cell Transplantation after Conditioning with Chidamide Plus Carmustine, Etoposide, Cytarabine, and Cyclophosphamide (Chi-BEAC) for Treatment of High-Risk and Relapsed/Refractory Aggressive Lymphoma: Multi-Center, Single-Arm, Open-Label Phase II Clinical Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 660-660
Author(s):  
Wei Xu ◽  
Yi Xia ◽  
Li Wang ◽  
Kaiyang Ding ◽  
Huayuan Zhu ◽  
...  
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Aggressive Lymphoma ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Relapsed Lymphoma ◽  
Third Line

Abstract Background: Chidamide, as a novel subtype-selective histone deacetylase inhibitors (HDACi), can directly inhibit tumor cell cycle progression and induce tumor cell apoptosis, inhibit phenotypic transformation of tumor cells and pro-drug resistance/pro-metastasis activity of the microenvironment, induce differentiation of tumor stem cells, and reverse epithelial-mesenchymal transformation of tumor cells, thereby restoring the sensitivity of drug-resistant tumor cells to drugs and enhancing the effect of chemotherapy agents through loosening chromatin and exposing DNA. The efficacy and safety of chidamide-BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide, Chi-BEAC) conditioning regimen combined with autologous stem cell transplantation (ASCT) were evaluated in a current phase II clinical trial for the treatment of high-risk and relapsed/refractory aggressive lymphoma. Methods: A total of 70 patients with high-risk diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), or mantle cell lymphoma (MCL) who had achieved complete remission (CR) or partial remission (PR) after first-line therapy or second-/third-line therapy were recruited from January 2018 to June 2021. Three of the patients were not evaluated after ASCT and two patients withdrew from the study; 65 patients were then evaluated for the effectiveness of Chi-BEAC treatment. Results: DLBCL and MCL are referred as B-cell non-Hodgkin lymphoma (B-NHL) and PTCL is referred as T and NK-cell non-Hodgkin lymphoma (T&NK-NHL) in the study. The median neutrophil engraftment time was 10 d (7-13 d) and median platelet engraftment time was 11 d (8-13 d). The CR rate at 3-6 months after transplantation was 75.4% in the 65 evaluable patients. The median progression free survival (PFS) and overall survival (OS) had not reached at the end of the follow-up period (median 18.1 month; range 1.8-42.0 months). The estimated PFS and OS at 24 months was 78.5% and 84.2%, respectively. Stratified analyses showed that in patients with B-NHL who previously received first-line treatment, the CR rate at 3-6 months after transplantation was 77.8%, and 2-year PFS was 74.8%. The survival rate might be better than previously reported for SWOG9704 (Stiff et al., 2013; PMID 24171516)-a 2-year PFS of 69%-and for DLCL04 (Chiappella et al., 2017; PMID 28668386)-a 2-year failure-free survival of 71%. In our patients with B-NHL who previously received second-/third-line treatments, the CR rate at 3-6 months after transplantation was 71.4%, and 2-year PFS was 77.1%. The survival rate might also be higher than previously reported for the CORAL trial (Gisselbrecht et al., 2010; PMID: 20660832), which showed a 2-year PFS of approximately 65%. In our patients with T&NK-NHL the CR rate at 3-6 months after transplantation was 73.3%, and 2-year PFS was 93.3%, The survival rate might be higher than previously reported for the NLG-T-01 trial (Francesco d'Amore et al., 2012; PMID: 22851556), which showed a 2-year PFS of approximately 55%. PFS stratification analysis showed that previous treatment outcomes affected the PFS: patients who had achieved CR before transplantation demonstrated better PFS than patients who had achieved PR (P = 0.199), while there was no significant difference between patients with different pathological subtypes (B or T&NK-NHL) or different risk groups. Most non-hematological adverse events (AEs) were of grade 1/2. Grade 4 AE only occurred in one patient, i.e., γ-glutamyl transpeptidase (GGT) elevation. Grade 3 AEs that occurred in ≥ 5% of the patients included febrile agranulocytosis (37.7%), hypokalemia (24.7%), hyponatremia (23.4%), GGT elevation (9.1%), and diarrhea (5.2%), which were well tolerated. Conclusions: This study showed that inclusion of the HDACi chidamide in conditioning regimen for ASCT greatly increased the PFS and OS, especially in patients with T&NK-NHL, and revealed an acceptable safety profile for refractory and relapsed lymphoma patients. Therefore, chidamide-containing conditioning regimen may be a great choice for patients with refractory and relapsed lymphoma, and awaits further confirmation by additional large-scale multi-center investigations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Adjuvant Gemcitabine-Oxaliplatin (GeMOX) after Curative Surgery in High-risk Patients with Cholangiocarcinoma

2009 ◽  
Vol 3 ◽  
pp. CMO.S3360
Author(s):  
Bernard Paule ◽  
Paola Andreani ◽  
Marie-Pierre Bralet ◽  
Catherine Guettier ◽  
René Adam ◽  
...  
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
High Risk Factors ◽  
Risk Patients ◽  
Disease Free Survival Rate ◽  
Disease Free

Background There is no standard adjuvant chemotherapy to prevent recurrent cholangiocarcinoma (CCA), a rare cancer with poor prognosis. We assessed the efficacy and safety of GEMOX on intrahepatic and hilar CCA with high-risk factors after curative surgery. Patients and Methods Twenty two patients (mean age: 57 years old) with CCA received 6 cycles of GEMOX: gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2, q3w after a curative surgery. Results All patients completed 6 cycles of GEMOX. EGFR membranous expression was present in 20 CCA. The 5-year survival rate was 56% (CI 95%: 25.7–85.4); 2-year disease free survival rate was 28% (CI 95%: 3.4–52.6). Median time to progression was 15 months. The rate of recurrence after surgery and chemotherapy was 63% (14/22). Two patients died of disease progression. Twelve patients received cetuximab/GEMOX at the time of relapse. Six died after 12 months (9–48 months), three are still alive suggesting a clinical applicability of EGFR inhibitors in CCA. Conclusion Adjuvant chemotherapy with GEMOX alone seems ineffective in intrahepatic and hilar CCA with a high risk of relapse. Additional studies including targeted therapies to circumvent such poor chemosensitivity are needed.

Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy

2012 ◽  
Vol 30 (28) ◽  
pp. 3533-3539 ◽  
Author(s):  
Arnauld Verschuur ◽  
Harm Van Tinteren ◽  
Norbert Graf ◽  
Christophe Bergeron ◽  
Bengt Sandstedt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
High Risk ◽  
Pulmonary Metastases ◽  
Stage Iv ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

scholarly journals Single High Intensity Focused Ultrasound Session as a Whole Gland Primary Treatment for Clinically Localized Prostate Cancer: 10-Year Outcomes

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ksenija Limani ◽  
Fouad Aoun ◽  
Serge Holz ◽  
Marianne Paesmans ◽  
Alexandre Peltier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
High Risk ◽  
High Intensity ◽  
Biochemical Recurrence ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Localized Prostate Cancer ◽  
Single Session ◽  
Free Survival

Objectives. To assess the treatment outcomes of a single session of whole gland high intensity focused ultrasound (HIFU) for patients with localized prostate cancer (PCa).Methods. Response rates were defined using the Stuttgart and Phoenix criteria. Complications were graded according to the Clavien score.Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients experienced biochemical recurrence for Phoenix and Stuttgart definition, respectively. The 5- and 10-year actuarial biochemical recurrence free survival rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%, respectively. Preoperative high risk category, Gleason score, preoperative PSA, and postoperative nadir PSA were independent predictors of oncological failure. 24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and 18.2% had acute urinary retention. A grade 3b complication occurred in 27 patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate was 30.8%.Conclusion. Single session HIFU can be alternative therapy for patients with low risk PCa. Patients with intermediate risk should be informed about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU performed very poorly in high risk patients.

Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5234-5234
Author(s):  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Stephen J. Schuster ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Tumor Cells ◽  
Platelet Transfusion ◽  
High Dose ◽  
Free Survival

Abstract Introduction: High-dose chemotherapy and autologous stem cell transplant (ASCT) can result in long term survival for patients with advanced non-Hodgkin’s lymphoma (NHL) but relapse remains a common cause of treatment failure. Bone marrow (BM) involvement is common in NHL and there is controversy over whether or not reinfusion of BM stem cells contaminated by clonogenic tumor cells is a major cause of relapse following ASCT. Bone marrow purging can reduce the number of tumor cells in vitro, but the impact on relapse and disease free survival (DFS) remains unknown. Methods: Between 1990 and 1993, 20 pts with poor prognosis NHL (B-symptoms, high LDH, bulky adenopathy, stage III or IV, or relapsed disease) at high risk for BM involvement underwent 4-hydroperoxycyclophosphamide (4-hc) purged BM transplantation. Thirteen pts had low grade B-cell NHL, 6 had an intermediate grade B-cell NHL with a small B-cell component, and 1 had T-lymphoblastic lymphoma. Seven of 20 pts had received ≥3 prior chemotherapeutic regimens. Three pts underwent transplantation in first complete remission and 17 pts were in chemotherapy-responsive relapse. At diagnosis, 11 of 20 pts had documented BM involvement, and at ASCT, 6 of 20 pts had BM involvement (all < 5% involvement at BM harvest). Eighteen pts (90%) received 4-hc purged autologous BM, and 2 pts (10%) received 4-hc purged autologous BM and peripheral stem cell support. High dose regimens included Cytoxan/TBI (85%), BCV(10%), and Melphalan/TBI (5%). The median age was 45 yrs (range: 20–57 yrs). The median nucleated cell count of 4-hc marrow that was reinfused was 2.4 × 108 /kg (range: 0.87–5.5). The median time to granulocyte recovery was 26 days (range: 14–59). Two pts died at days 31 and 35 without achieving platelet transfusion independence. In the remaining 18 pts, the last platelet transfusion was given at a median of 29 days post-marrow infusion (range 18–149), and the median in-patient hospital days was 27 (range: 16–82 days). Results: There were 2 deaths (fungal infection and CNS relapse) during ASCT. One pt died in CR after developing secondary AML 5.34 yrs after ASCT. Post-ASCT, 18 of 20 pts achieved CR (including 1 pt who had no evidence of disease at autopsy), 1 pt had a PR, and 1 pt died during BMT and was not evaluable for response. Median follow-up for the group was 8.2 yrs (range: 0.1–12.4 yrs). At last follow-up, 9 pts remain in CR (1 died of AML in CR), 5 pts had relapsed and remain alive, and 5 pts died of progressive disease. Median follow-up for survivors was 11.1 yrs (range: 5.2–12.4 yrs). 65% of pts remain alive at last follow-up. The median EFS was 9.4 yrs (range: 0.1–12.4 yrs). Those who achieved a CR post-ASCT had a median DFS of 10.6 yrs (range: 1.1–12.4 yrs). At 8.2 yrs, 4/6 pts with involved BM at the time of harvest had relapsed or died compared to 7/14 pts with negative BM which is not significantly different. Conclusion: ASCT using 4-hc BM purging is feasible and can result in long term relapse free survival, even for pts with subtypes of NHL at high risk for BM involvement. Whether 4-hc BM purging is equivalent or superior to immunologic approaches to stem cell processing remains to be determined.

Cytarabine Either with Induction or Conditioning May Improve Outcomes Among Those Undergoing Autologous Transplantation in First or Second Remission for Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4546-4546
Author(s):  
Bijal D. Shah ◽  
Bryan J Little ◽  
Jennifer Cultrera ◽  
Celeste M. Bello ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Published Data ◽  
Free Survival ◽  
Improve Outcome ◽  
Significant Difference ◽  
Mantle Cell

Abstract Abstract 4546 Introduction: Consolidation with autologous transplantation (AutoSCT) may extend progression free survival when administered following initial induction. Published data suggest intensive cytarabine containing induction may improve outcome when administered prior to autologous transplantation. Methods: We retrospectively evaluated all patients with MCL transplanted at our institution before 2010. We identified 57 patients, among whom 52 were transplanted in first or second remission. Results: 21 patients had received a cytarabine containing induction (most commonly R-HyperCVAD), among whom 14 also received cytarabine as a component of conditioning (BEAM+/−R). The most common induction in the remaining patients was R-CHOP. Among the 31 who did not receive a cytarabine based induction, 23 received cytarabine as a component of the pre-transplant conditioning regimen (BEAM+/−R). The median PFS for those getting cytarbine with induction and conditioning was approximately 28 months (at which time 51% of patients continued without progression). The median PFS for those getting cytarabine with conditioning only was approximately 38 months (at which time 47% continued without progression). Logrank analysis shows no statistically significant difference between these groups (p one-sided = 0.29). Alternatively, those who did not receive any cytarabine had a median PFS of 20 months, with no survival beyond 33 months. Logrank analysis shows this to be inferior to those receiving cytarabine with induction/conditioning (p one-sided = 0.049), as well as among those who received cytarabine with conditioning only (p one-sided = 0.001). Conclusions: In the absence of randomized comparisons it is difficult to draw firm conclusions on the role of induction. These analyses would suggest that among those with chemosensitive disease able to proceed to transplant, more modern conditioning with cytarabine containing regimens may make up for lack of exposure to this agent during induction. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.

Nodal Peripheral T-Cell Lymphoma – a Clinical and Epidemiological Analysis at Medicine School of Sao Paulo University

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1706-1706
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Marianne Castro Goncalves ◽  
Rodrigo Santucci ◽  
Renata Oliveira Costa ◽  
Debora Levy ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
Large Cell Lymphoma

Abstract Background: Peripheral T-cell lymphoma (PTCL) are a biologically and clinically heterogeneous group of rare diseases arising from mature or activated post-thymic T lymphocytes. Correspond to 10% to 15% of lymphoid malignancies with marked geographical variation in incidence. According to the WHO classification they are divided into nodal, extranodal, primary cutaneous and leukemic or disseminated and encompass 18 distinct entities. The nodal group involves the peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic lymphoma (AITL), anaplastic large cell lymphoma ALK positive (ALCL-ALK+) and anaplastic large cell lymphoma ALK negative (ALCL-ALK-). The literature of PTCL is scarce, especially in our country where data of epidemiology, clinical features and outcomes are usually rarely available. So, to better understand PTCL we performed a retrospective study with patients treated in a reference service for cancer treatment in Brazil. Methods: Eight-seven nodal PTCL patients treated with anthracyclne-based regimen (CHOP or, CHOEP) from January 2000 to June 2014 were evaluated retrospectively at the Medicine School of Sao Paulo University, Brazil. All patients lower than 60 years were consolidated with autologous hematopoietic stem cell transplantation (ASCT) in first CR or PR except that with ALCL-ALK+ diagnosis. Refractory and relapsed patients were salvaged with 3-4 cycles of IVAC (Ifosphamide 1.5 g/m2 i.v D1-D5, etoposide 100mg/m2 i.v D1-D5, aracytin 2g/m2 i.v twice a day D1-D2) regimen and submitted to ASCT. It was performed a central histopathological review and clinical and epidemiological data were obtained from medical records. Patients were evaluated for overall response (OR) including complete response (CR) and partial response (PR), overall survival (OS) and progression free survival (PFS). Statistical analysis was performed using the STATA-3 program using and a p-value ≤ 0.05 was considered statistically significant. Results: Of the 87 patients, 34 (39.08%) cases were classified as ALCL-ALK-, 27 (31.03%) as PTCL-NOS, 16 (18.39%) as ALCL-ALK+, 6 (6.89%) as AITL and in 4 (4.1%) cases the diagnosis could not be performed and an expansion of the immunohistochemical is ongoing. Thirty-six (45.38%) cases were female and 51(54.62%) were male, 59(67.81%) patients were lower than 60 years. Seventy-six (87.35%) patients presented in advanced stage (III or IV) at diagnosis but 73(83.90%) patients presented an ECOG < 2 and 14(16.10%) ≥ 2. Eighteen (20.70%) patients were of low-risk, 26 (29.88%) of low-intermediate risk and 43(49.42%) of high-intermediate and high-risk of international prognostic index (IPI). The CR and PR was obtained for 44(50.57%) and 8(9.19%), respectively with 59.76% OR. Thirty (34.48%) patients were primary refractory and five remain under treatment. In a median of follow of 30 months, ALCL-ALK+ show higher OS (median 140.98 months) than ALCL-ALK- (44.20 months), PTCL-NOS (median 20.62 months) and AITL (median 7.24 months) (p=0.41) (Figure 1A). The median of PFS was 3.84 months for AITL, 23.44 months for ALCL-ALK+, 40.03 months for PTCL-NOS and was not yet reached for ALCL-ALK- (p=0.0006) (Figure 1B). Figure 1: Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 1:. Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 2 Figure 2. Conclusion: In this study we showed that ALCL-ALK+ as well as found in the literature presented a better OS in comparison to others nodal T-cell lymphoma as AITL, PTCL-NOS and ALCL-ALK-. Surprisingly the PFS of ALCL-ALK+ was statistically significant lower than of ALCL-ALK-. We thought that this result may be explained because in our service until to perform this analysis we did not indicate ASCT in first CR for ALCL-ALK+, but for all ALCL-ALK-. This hypothesis may be reinforced as the most of our cases presented high-intermediate and high-risk of IPI and that could equalize the favorable effect of ALK expression. In addition, we changed our approach and we are also indicating ASCT in first line for patients with ALCL-ALK+ with intermediate-high and high-risk of IPI . Disclosures No relevant conflicts of interest to declare.

Unrelated Donor KIR B/X Genotype Reduces Relapse and Improves Progression-Free Survival after HLA-Matched Allogeneic Transplantation for Relapsed/Refractory Non-Hodgkin Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 670-670
Author(s):  
Veronika Bachanova ◽  
Daniel J. Weisdorf ◽  
Tao Wang ◽  
Steven G.E. Marsh ◽  
Elizabeth Trachtenberg ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Nk Cells ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Unrelated Donor ◽  
Advisory Committees ◽  
Free Survival ◽  
Kir Genes ◽  
Non Hodgkin Lymphoma

Abstract While allogeneic donor hematopoietic cell transplantation (HCT) can cure non-Hodgkin lymphoma (NHL) by inducing a graft-versus-lymphoma effect, 10-35% of patients experience progression or relapse. We investigated whether the genotype of allogeneic donor natural killer (NK) cell killer immunoglobulin-like receptors (KIR) impacts the survival of lymphoma patients. The importance of KIR genetics in unrelated donor (URD) HCT has been demonstrated in AML where donors with favorable KIR gene content reduced the risk of relapse by 30%. Because the consequence of donor KIR genotype in NHL is unknown, we evaluated its effect on transplant outcome in 614 adults with NHL (28% follicular lymphoma, 16% diffuse large B cell lymphoma, 17% mantle cell lymphoma, 37% other) who underwent T cell replete URD HCT between 1990-2009 with outcomes reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Donor samples from the NMDP/CIBMTR Repository were genotyped (15 KIR genes) by MALDI-TOF mass spectroscopy. KIR haplotypes (A/A or B/x) were determined by presence/absence of individual KIR genes. Multivariate regression models were used to test the associations between donor KIR genotype and clinical outcome. The median patient age was 50 years (range 19-72), 93% were Caucasians and 62% had chemosensitive lymphoma. Most (60%) were >1.5 years from diagnosis; 41% received myeloablative preparative regimens and 61% received peripheral blood derived grafts. Most transplants were 10/10 matched for HLA alleles (n=396), the remainder 9/10 matched (n=158) or ≤8/10 matched (n=60). The frequencies of KIR genotypes in donors reflected the Caucasian population: 70% (n=428) were KIR B/x and 30% (n=180) were KIR A/A. Patients receiving 10/10 HLA-matched grafts (65%) experienced significantly lower relapse at 5 years when donors were KIR B/x genotype (n=281; 26% [95%CI 21-32%]) compared to KIR A/A genotype (n=115; 37% [95% CI 27-46%] ;p=0.05; Figure left) leading to improved progression-free survival (PFS) (35% [95% 26-44] vs. 22% [95%CI 11-35%]; p=0.02; Figure right). After adjusting for significant clinical variables, KIRB/x donors conferred significant protection against relapse (RR 0.63 [95%CI 0.43-0.92]; p=0.02) and improved PFS (RR 0.71 [95% CI 0.55-0.91]; p=0.008) compared to KIR A/A donors. The relapse protection and improved survival associated with KIR B/x donors was highly significant in the 10/10 HLA matched cohort (n=396) but not in the HLA-mismatched transplants (n=218; PFS RR 1.21 [95%CI 0.86-1.7]; Relapse RR 1.49 [0.87-2.55], p=NS for both). Importantly, the use of KIR B/x donors was associated with improved clinical outcomes for patients after both myeloablative and reduced intensity conditioning. Donor KIR genotype had no effect on rates of acute graft-versus-host disease (HR 1.05; p=0.86), and treatment related mortality at 1 year was similar for both groups (28% [B/x] and 30% [A/A]). In multivariate analysis of the entire cohort, other factors adversely impacting PFS included chemoresistant lymphoma (HR 1.52; p=0.03), disease other than follicular lymphoma (HR 1.34; p=0.0001) and <1.5 years interval from diagnosis to HCT (HR 1.35; p=0.003). Our results demonstrate that donors with KIR B/x genotypes, whose NK cells express more activating KIR, are associated with decreased relapse and improved survival after 10/10 HLA-matched URD HCT for NHL. The results suggest that NK cells may contribute to graft-versus-lymphoma effects and support the consideration of KIR genotyping with HLA typing into URD search criteria for patients with NHL. Figure 1 Figure 1. Disclosures Miller: Coronado: Speakers Bureau; BioSciences: Membership on an entity's Board of Directors or advisory committees; SAB: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1202-1210 ◽  
Author(s):  
Nozomi Niitsu ◽  
Junko Okabe-Kado ◽  
Masataka Okamoto ◽  
Toshiyuki Takagi ◽  
Takashi Yoshida ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Number Of Patients

Advances in chemotherapy have led to a favorable long-term prognosis in approximately 50% of patients with aggressive non-Hodgkin lymphoma (NHL). However, the remaining patients do not enjoy such prolonged survival after standard treatment. New prognostic factors are needed to define this poor-prognosis group and to plan an appropriate treatment strategy. It has been reported that serum nm23-H1 protein may be a new prognostic factor for aggressive NHL. In the present study involving multiple institutions and a large number of patients, the level of nm23-H1 protein was compared among different types of lymphoma; it was lowest for indolent lymphoma, followed by aggressive lymphoma and then highly aggressive lymphoma. In addition, patients with aggressive NHL and higher nm23-H1 levels had worse overall and progression-free survival rates than those with lower nm23-H1 levels. The nm23-H1 level was also compared between patients with diffuse large B-cell lymphoma and patients with peripheral T-cell lymphoma. The results suggest that the level of nm23-H1 could serve as a prognostic factor in both groups. Moreover, the prognosis of lymphoma patients could be ascertained even more precisely by combining soluble interleukin-2 receptor or soluble CD44 and nm23-H1 levels. A multivariate analysis confirmed that the nm23-H1 level is an independent and important prognostic factor in aggressive NHL. Therefore, it may provide useful information for clinicians to determine the appropriate therapy for each type of lymphoma.

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