Immunochemotherapy with Rituximab Improves Molecular CR Rate and Outcome In CD20+ B-Lineage Standard and High Risk Patients; Results of 263 CD20+ Patients Studied Prospectively In GMALL Study 07/2003

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 170-170 ◽  
Author(s):  
Dieter Hoelzer ◽  
Andreas Huettmann ◽  
Felix Kaul ◽  
Sebastian Irmer ◽  
Nadja Jaekel ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Relapse Rate ◽  
Remission Rate ◽  
Supportive Therapy ◽  
High Risk Patients ◽  
Tumour Load ◽  
Risk Patients ◽  
Standard Risk

Abstract Abstract 170 The effect of Rituximab in conjunction with a chemo induction and consolidation therapy was studied in CD20+, Ph/BCR-ABL negative B-precursor ALL (Pre-B/Common) in the GMALL Study 07/2003. The rationale were encouraging results with combined intensive chemotherapy and Rituximab in CD20+ adult Burkitt lymphoma / leukemia. Furthermore that in previous GMALL studies, improvement of B-precursor ALL by intensification of chemotherapy was limited and the observation that patients with CD20+ cells (antigen expression >20%) had an inferior outcome in adult ALL (Thomas et al. Blood 2009. 113;6330). Aim: In standard risk (SR) patients the aim was to increase the rate of molecular remission (Mol. CR) thereby decreasing the relapse rate and in high risk (HR) patients to reduce the pre-transplant tumour-load and thereby reducing the relapse rate after SCT which was 30–40% in previous GMALL studies. Materials and Methods: Adult ALL patients (15 – 55 years) with standard risk B-precursor ALL being CD20 pos. received Rituximab 375 mg/m2 at day -1 before each induction course (phase I and II), the re-induction course and before each of the six consolidations for a total of 8 doses. High Risk patients, defined as WBC > 30.000 and/or late CR > 4 weeks, which are candidates for a stem cell transplantation in CR 1 after wk 16, received Rituximab three times (d -1 ind. I/II and Cons. I) before SCT. Patients receiving Rituximab were compared with earlier CD20+ patients in the GMALL study 07/2003 with identical chemo- and supportive therapy but no Rituximab. MRD method and chemo backbone was described earlier [Brüggemann, Blood 2006: 107;1116]. Results: A total of 263 CD20 pos. patients were analyzed in the GMALL study 07/2003; 196 were SR and 67 HR patients. 181 received Rituximab (R+ arm) and were compared to a cohort of 82 patients earlier recruited without Rituximab (R- arm). In the SR there was no difference in the results of induction therapy with a CR rate of 94 % and 91 % in the R+ vs. R- patients. There was also no difference in ED rate 5% vs. 3% or failure/PR 1% vs. 5%. However, MRD course differed substantially. Decrease in MRD load in the R+ vs. R- arm was faster with a Mol CR (MRD <10-4) rate of 57% vs. 27% at day 24 and of 90% vs. 59% at wk 16. Probability for continuous complete remission (CCR) at 5 years was 80% vs. 47% for R+ vs. R- pts. and for overall survival 71% vs. 57%. In the cohort of 67 HR patients the CR rate for R+ vs. R- was 81% vs. 88% due to a higher rate of failure/PR 12% vs. 8%. The ED rates in the R+ vs. R- arm were 7% vs. 4%. There was a higher Mol CR rate at wk 16 in the R+ arm vs. R- with 64% vs. 40%. Overall survival for HR patients at 5 yrs was 55% vs. 36% in the R+ vs. R- group. When only the HR cohort with SCT in CR1 is considered (in 69 % +R and 90% -R SCT in CR1 were performed) the CCR probability was superior for the R+ vs. R- with 67% vs. 37%, due to a lower relapse rate. Conclusion: Intensive chemo- plus immunotherapy with Rituximab is feasible in adult patients with B-precursor ALL in the context of the GMALL protocol 07/2003. In standard risk patients, the complete remission rate was comparable. There was however a faster and higher Mol. CR rate in the Rituximab cohort, with an improvement in remission duration and overall survival. In high risk patients the Mol. CR rate was also higher in the R+ arm and the relapse rate after SCT lower, but probably more Rituximab doses are needed in this patient cohort to reduce the tumour load before SCT further. Supported by Deutsche Krebshilfe 70–2657-Ho2 and in part by Hoffmann La Roche. Disclosures: Off Label Use: Rituximab: activity against CD20 pos. ALL cells.

scholarly journals Epidemiological characteristics and survival outcomes of children with medulloblastoma treated at the National Cancer Institute (INCA) in Rio de Janeiro, Brazil

2020 ◽  
Author(s):  
Gabriela Oigman ◽  
Diana Osorio ◽  
Sima Ferman ◽  
Joseph Stanek ◽  
Antonio Aversa ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
High Income ◽  
Survival Outcomes ◽  
Middle Income ◽  
Female Ratio ◽  
High Risk Patients ◽  
Risk Patients ◽  
Epidemiological Characteristics ◽  
Standard Risk

BACKGROUND: Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. METHODS: Retrospective review of 114 children (3-18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS: The male/female ratio was 1.32 and the median age at diagnosis was 8.2 years. Headache (83%) and nausea/vomiting (78%) were the most common presenting symptoms. Overall survival (5y) was 59,1% and EFS (5y) was 58,4%. The OS for standard-risk patients was 69% and 53% for high-risk patients. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.25). Patients who lived >40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS: The epidemiological characteristics of this series possibly explain the differences in survival that medulloblastoma patients have in Brazil. Issues related to limited health care resources, poverty, delayed diagnosis, treatment abandonment, and malnutrition are reflected in inferior survival outcomes when compared to high-income countries. Despite the difficulties encountered in an upper-middle income country, it was possible to deliver treatment with good results.

In Adults with Standard-Risk Acute Lymphoblastic Leukemia (ALL) the Greatest Benefit Is Achieved from an Allogeneic Transplant in First Complete Remission (CR) and an Autologous Transplant Is Less Effective Than Conventional Consolidation/Maintenance Chemotherapy: Final Results of the International ALL Trial (MRC UKALL XII/ECOG E2993).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2-2 ◽  
Author(s):  
Jacob M. Rowe ◽  
Georgina Buck ◽  
Adele Fielding ◽  
Martin S. Tallman ◽  
Alan K. Burnett ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Relapse Rate ◽  
Allogeneic Transplant ◽  
No Donor ◽  
High Risk Patients ◽  
Autologous Transplant ◽  
Sibling Donor ◽  
Risk Patients ◽  
Standard Risk

Abstract MRC UKALL XII / ECOG E2993 was initiated in 1993, to prospectively define the role of allogeneic transplant (allo), autologous transplant (auto) or chemotherapy in adult ALL in first CR up to age 60 (65 since 2004). All patients received two phases of induction and, if in CR, patients <50 yrs (55 since 2004) were assigned to allo if they had a compatible sibling donor. The other patients were randomized to consolidation/maintenance therapy (chemo) for two and a half years or a single autologous transplant. Prior to the assigned or randomized therapy all patients received intensification with 3 courses of high-dose methotrexate. Over 1,980 patients have been entered on study. The data on induction for all patients and post-remission for Ph-positive ALL were previously reported (Blood.2005;106:3760 and Blood.2003; 104:268a). This report describes the post-remission data for Ph-negative patients entered as of October 31, 2005. The data are summarized in the table. High-risk patients are those with either age > 35 or a high WBC (>30,000 for B-lineage or >100,000 for T-ALL). In a donor versus no donor analysis, patients with a sibling donor had improved OS and EFS and the relapse rate post allo was very significantly lower than for any other therapy. However, this advantage was confined to standard-risk patients. The lack of demonstrable survival benefit in high-risk patients was due to high mortality associated with age >35 years; the 2-year non-relapse mortality for patients with a donor was 39% (high-risk) and 20% (standard-risk) compared with 12% (high-risk) and 7% (standard-risk) among those without a donor. In an intention-to-treat analysis of chemo versus auto, patients receiving chemo had significantly better EFS. The difference between these 2 groups was not due to a higher mortality of auto but due to a higher relapse rate. Molecular monitoring of minimal residual disease (MRD) after induction phase II and intensification was highly predictive of outcome among the non-allo patients (OS 70% vs 22%; p=.0012). In summary, the data demonstrate that sibling allogeneic transplants for ALL in CR1 provide the most potent anti-leukemic therapy and considerable OS and EFS benefit for standard-risk patients. In contrast, the transplant-related mortality for high-risk older patients was unacceptably high and abrogated the reduction in relapse risk. Furthermore, the data show that there is no evidence that a single auto can replace consolidation/maintenance therapy in any risk group. Large collaborative trials are necessary, and feasible, to define the optimal therapy in uncommon disorders. 5-year data No. of Patients OS (%) EFS (%) Relapse (%) * P = < .05 ** Autograft patients excluded Donor vs no donor 388 vs 527 *53 vs 45 *50 vs 41 *29 vs 54     High risk 170 vs 230 39 vs 36 38 vs 32 *36 vs 63     Standard-risk 218 vs 286 *63 vs 51 *59 vs 48 *25 vs 48 Randomized auto vs chemo 220 vs 215 37 vs 46 *33 vs 42 *61 vs 54 Donor vs no donor (chemotherapy)** 384 vs 418 *54 vs 44 *50 vs 40 *29 vs 55     High-risk 168 vs 190 41 vs 35 38 vs 31 *36 vs 63     Standard risk 216 vs 223 *64 vs 51 *59 vs 47 *24 vs 48

scholarly journals LINC-28. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH MEDULLOBLASTOMA TREATED AT THE NATIONAL CANCER INSTITUTE (INCA) IN RIO DE JANEIRO, BRAZIL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii383-iii384
Author(s):  
Gabriela Oigman ◽  
Diana Osorio ◽  
Joseph Stanek ◽  
Jonathan Finlay ◽  
Denizar Vianna ◽  
...  
Keyword(s):  
High Risk ◽  
Maternal Education ◽  
Survival Outcomes ◽  
Middle Income ◽  
Female Ratio ◽  
High Risk Patients ◽  
Presenting Symptoms ◽  
Risk Patients ◽  
Epidemiological Characteristics ◽  
Standard Risk

Abstract BACKGROUND Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. Brazil is an upper-middle income country according to World Bank, with features of LMIC and HIC. METHODS We conducted a retrospective review of 126 children (0–18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively; overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS The male/female ratio was 1.42 and the median age at diagnosis was 7.9 years. Headache (79%) and nausea/vomiting (75%) were the most common presenting symptoms. The median time from onset of symptoms to surgery was 50 days. The OS for standard-risk patients was 69% and 53% for high-risk patients. Patients initiating radiation therapy within 42 days after surgery (70.6% versus 59.6% p=0.016) experienced better OS. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.025). Patients who lived &gt;40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS These findings suggest that socioeconomic factors, education, early diagnosis and continuous data collection, besides oncological treatment must be adressed to improve the survival of children with MB.

Quality of Life and Overall Survival in High Risk Patients After Radical Cystectomy With a Simple Urinary Derivation

2015 ◽  
Vol 93 (6) ◽  
pp. 368-374
Author(s):  
Giuseppe Mucciardi ◽  
Luciano Macchione ◽  
Alessandro Galì ◽  
Antonina di Benedetto ◽  
Enrica Subba ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
High Risk ◽  
Radical Cystectomy ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations

2018 ◽  
Vol 36 (15) ◽  
pp. 1486-1497 ◽  
Author(s):  
Sylvie D. Freeman ◽  
Robert K. Hills ◽  
Paul Virgo ◽  
Naeem Khan ◽  
Steve Couzens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
High Risk Factors ◽  
Risk Patients ◽  
Standard Risk ◽  
Acute Myeloid

Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD−. Patients without high-risk factors, including Flt3 internal tandem duplication wt/− NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD−; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD−, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD− (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.

Outcome of Adult AML at First Relapse Following a Risk-Oriented Strategy: An Update of the Northern Italy Leukemia Group (NILG) Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4385-4385 ◽  
Author(s):  
Irene Cavattoni ◽  
Enrico Morello ◽  
Elena Oldani ◽  
Tamara Intermesoli ◽  
Ernesta Audisio ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Risk Category ◽  
High Dose ◽  
High Risk Patients ◽  
Risk Patients ◽  
First Relapse ◽  
Group 2 ◽  
Standard Risk ◽  
Group 1

Abstract INTRODUCTION The impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) was retrospectively analyzed in 172 patients (patients) with relapsed non-APL AML, who had been initially treated with standard induction and risk-adapatiented consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All 172 patients were at first recurrence following consolidation of CR1 with high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinical-cytogenetic criteria) or allo-SCT in case of high-risk prognostic profile. Median age at relapse was 55 y (range 21–70). CR1 duration was &lt;6 months in 50 patients (29%), ranging from 0.6 to 52,7 mo (median 9,1). High risk patients were 128/172 (74%) and 43/172 patients (25%) had an unfavourable cytogenetics (CG). One hundred-eleven patients (64%) received HiDAC and 24 (14%) an allo-SCT according to study design. RESULTS 140 patients (81%) received salvage treatment. The remaining 32 patients (19%) received palliation and all of them died. The median OS was 17.1 mo, with a 2yOS of 34%. Favorable prognostic factors identified by univariate analisys were: favourable or intermediate CG (p=0,007), standard risk category according to first line protocol (p=0.004), availibility of a HLA matched donor (p= 0.048), achievement of an early CR1(p=0,000), HiDAC as first line therapy(p=0,000), alloHSCT perfomed at relapse (p=0,000) and a DFS from CR1&gt;12 mo (p=0,000). In multivariate analysis favourable or intermediate CG and DFS &gt;12 mo were confirmed as independent prognostic factors (p=0,036 and p=0,001 respectively). Among the 140 patients, 50 received an allo-SCT following relapse (36%, group 1), and the remaining 90 (64%, group 2) received high dose chemotherapy alone (85), autologous SCT (2), or DLI (3, in case of previous alloSCT). Both groups were comparable regarding age &gt;55 y, prior allo-SCT and risk class at diagnosis. After salvage therapy, 44 patients(88%) in the group 1 achieved CR2, compared to 26 patients (29%) in the group 2. The median duration of CR2 was 9 mo (range 2–64) and 3 mo (range 1–34) in group 1 and 2 respectively. NRM was 17/140: 12 patients (24%) in the allo-SCT group and 5 (6%) in group 2. The 2yOS was 57% and 23% respectively (p=0,000). Moreover, among 50 alloSCT patients, survival was affected by risk category at diagnosis: 2yOS of 19 (38%) standard risk patients was 83% compared to 42% in 31 high risk patients (62%) (p=0.01). This risk stratification has no impact on OS in the group 2. CONCLUSIONS DFS &gt; 12 mo and standard risk category at diagnosis, according to NILG protocol, are the most important independent positive prognostic factors impacting OS of AML relapsed patients. The availibility of a HLA matched donor and a subsequent intensification with alloSCT may offer substantial salvage rates and its outcome is affected by the risk stratification at diagnosis. Nevertheless, high risk patients could benefit from alloSCT, reaching an 2yOS of 42%.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

Regular Prophylactic Donor Lymphocyte Infusion Is Effective and Safe to Prevent Relapse after Hematopoietic Cell Transplantation in High-Risk Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3439-3439
Author(s):  
Yi Luo ◽  
Yamin Tan ◽  
Yongxian Hu ◽  
Jimin Shi ◽  
Weiyan Zheng ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Relapse Rate ◽  
Hematopoietic Cell Transplantation ◽  
Donor Lymphocyte Infusion ◽  
Unrelated Donor ◽  
Relapse Risk ◽  
Risk Patients ◽  
Risk Of Relapse

Abstract Background Donor lymphocyte infusion (DLI) is the mainstream therapy for the prevention and treatment of relapse following hematopoietic cell transplantation (HCT). The efficacy of DLI for patients with acute leukemia, however, is limited in previous studies. This may be due to the more rapid proliferative capacity of malignant cells in acute leukemia, since a full response to DLI often requires months. Moreover, DLI is more effective when there is less disease burden to eradicate. Therefore, patients with high risk of relapse may take advantage of an early DLI after HCT. In this study, we applied an early prophylactic DLI in high relapse-risk patients with negative MRD (MRD-) after HCT. Patients and Methods From July 2013 to December 2015, 56 adult patients with high relapse-risk in our center were admitted in this study. High relapse-risk was defined as failure to attain a complete remission (CR) after two cycles of induction therapy (primary induction failure), more than second complete remission (¡ÝCR2), no complete remission before HCT, or increasing MRD before HCT detected by flow cytometry (FCM) or real-time quantitative PCR (RQ-PCR). All patients received modified busulfan/cyclophosphamide¨Cbased myeloablative conditioning regimen. Rabbit antithymocyte globulin was administered for patients receiving unrelated donor HCT or haploidentical HCT. All patients received graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine A, methotrexate and low-dose mycophenolate mofetil. Post-HCT MRD was monitored at regular intervals with FCM or RQ-PCR. All patients achieved negative MRD post-HCT in our study. Results In total, 56 patients (median age, 36, range, 17-46; 66.1% male) with high relapse risk were included in our study. 15 patients had acute lymphoblastic leukemia; 25 had acute myeloid leukemia; 5 had chronic myelogenous leukemia blast phase; the rest hadT-cell lymphoblastic lymphoma, myelodysplastic syndromes with refractory anemia with excess blasts-2, and peripheral T-cell lymphoma. Among them, 37 (66.1%) received haploidentical-HCT, 16 (28.6%) received matched sibling donor-HCT, and three (5.4%) received unrelated donor-HCT. The median time from HCT to DLI was 82 days (range, 47-160). After a median follow-up of 21 months (range, 7-34), the overall survival (OS) at two years was 78.4%; the disease-free survival (DFS) at two years was 75.4%, with relapse rate of 13.3%. Clinical characteristics were subjected into univariate Cox analysis for OS or relapse rate to find prognostic factors. Neither donor type nor disease type had significant impact on OS or relapse rate in our study. Of note, four patients relapsed after the first DLI underwent chemotherapy combined with a second DLI. Unfortunately, this strategy failed to treat relapse in all of the four patients. The main concern following DLI is the emergence of GVHD. In our study, 19 of the 56 patients (33.9%) developed aGVHD after DLI, mostly Grade I to Grade II (n = 15, 78.9%). cGVHD was observed in 25 of the 56 patients (44.6%), mostly with limited manifestations (n = 20, 80%). Among the deceased 11 patients, only one patient died secondary to GVHD complications due to bronchiolitis obliterans. Conclusions For patients with high risk of relapse following HCT, this study indicates that early administration of DLI is effective and safe to prevent relapse. Regular application of DLI for negative MRD patients post-HCT with high relapse risk may be a feasible strategy to prevent future relapse. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Real-World Clinical Outcomes By Cytogenetic Risk Category in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4784-4784
Author(s):  
Huamao Mark Lin ◽  
Keith L Davis ◽  
James A. Kaye ◽  
Katarina Luptakova ◽  
Lu Gao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Partial Response ◽  
Research Funding ◽  
Complete Response ◽  
Line Treatment ◽  
Second Line ◽  
High Risk Patients ◽  
Risk Patients ◽  
Standard Risk

Abstract INTRODUCTION: Multiple Myeloma (MM) is an incurable hematologic cancer characterized by multiple recurrences. With each recurrence, patients have a lower probability of response and duration of response is shorter. Therefore, there is an unmet need to improve outcomes in relapsed/refractory multiple myeloma (RRMM). There is a shortage of data describing clinical features and outcomes in these patients in real-world practice, particularly with regard to differences in outcomes by baseline cytogenetic risk. To help address this information gap, this study analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective observational review of medical records was conducted in a cohort of 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients could be alive or deceased at the time of record abstraction. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were assessed for treatment response, overall survival (OS) and progression-free survival (PFS) from date of first relapse (study index date). All analyses were descriptive. Survival was assessed using the Kaplan-Meier (K-M) method. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. A total of 55 high-risk and 113 standard-risk patients were identified; risk category was unknown or unassessed for 32 patients. Among all patients, mean (SD) age at RRMM diagnosis was 66.3 (8.9) years and 62% of the sample was male. Lenalidomide + dexamethasone was the most common second-line systemic regimen initiated (50% of high-risk patients, 59.5% of standard-risk patients receiving second-line treatment). A total of 114 patients (57%) initiated a third-line treatment. Despite clinical response in second-line treatment occurring sooner in high-risk patients (median: 106 days) than in standard-risk patients (median: 237 days), physician-assessed overall response rate (ORR) was lower in high-risk patients (63%: 17% complete response, 46% partial response) than standard-risk patients (91%: 26% complete response, 65% partial response) across all second-line treatments combined (Table 2).. For third-line treatment, ORR was lower in high-risk patients (54%: 12% complete response, 42% partial response) than standard-risk patients (74%: 9% complete response, 65% partial response). Among patients who initiated a second-line treatment (n = 192), 47.4% were deceased at the time of data collection. From second-line initiation, K-M estimates of 1- to 5-year OS and PFS were substantially lower for high-risk patients versus standard-risk. Specifically, the proportions of patients still alive 1, 3, and 5 years after second-line treatment initiation were 73%, 51%, and 36%, respectively, for high-risk patients and 94%, 73%, and 61% for standard-risk patients. The proportions of patients without disease progression at 1, 3, and 5 years after second-line initiation were 48%, 13.5%, and 5% for high-risk patients and 82%, 42%, and 14% for standard-risk patients. CONCLUSIONS: The importance of cytogenetic risk classification as a prognostic factor in RRMM was apparent in this retrospective review, in which patients with high-risk cytogenetics had less favorable outcomes in terms of ORR, OS, and PFS than standard-risk patients. Decreased response rate and lower PFS and OS was documented among patients with high-risk cytogenetics, which is in contrast to shorter time needed to achieve best clinical response in this subgroup. Results from this real-world study provide further confirmation of the unmet medical need presented by RRMM, especially for patients with high-risk cytogenetics. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

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