scholarly journals Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children's Oncology Group

2016 ◽  
Vol 64 (4) ◽  
pp. e26278 ◽  
Author(s):  
Cindy L. Schwartz ◽  
Lu Chen ◽  
Kathleen McCarten ◽  
Suzanne Wolden ◽  
Louis S. Constine ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3649-3649 ◽  
Author(s):  
Cindy Schwartz ◽  
Lu Chen ◽  
Louis Constine ◽  
Suzanne Wolden ◽  
Frank G Keller ◽  
...  

Abstract Abstract 3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis. Background: Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach. The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population. 1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children's Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this report. Methods: Patients <21 years with intermediate risk HL were eligible for COG AHOD0031. The study evaluated the tailoring of treatment by early response to 2 ABVE-PC. Rapid early response (RER) was a 2-dimensional tumor reduction of >60% after 2 cycles of ABVE-PC. Complete response (CR) was a >80% 2-diminsional reduction by CT, and resolution of nuclear imaging abnormalities. RER who achieved CR after 2 additional ABVE-PC were randomized to +/− 21Gy. Slow early responders (SER) were randomized to +/− DECA in addition to the 4 ABVE-PC/21 Gy. Cox regression analysis was used to evaluate potential predictors of EFS (gender, age, race, stage, mediastinal mass, B symptoms, hemoglobin, sedimentation rate, albumen, histology). Continuous variables were dichotomized by clinical significance or quartiles of the population. Multivariable predictive modeling was performed using univariate predictors with a p<0.25. In instances of collinearity, the most robust variable was used. A stepwise selection algorithm was used to identify predictors with a p<0.15. Results: Four predictors (stage 4, large mediastinal adenopathy, albumen<3.5 and fever) were identified as predictive of adverse EFS. Since the Hazard Ratios were similar, the CHIPS (Childhood Hodgkin IPS) score was devised that gave 1 point for each of the 4 adverse predictors. EFS based on score was found to predict an excellent outcome of nearly 90% for those with CHIPS 0 or 1 (N=589) vs. 78% or 62% for those with CHIPS 2 or 3 respectively (N= 141 and 32). Conclusion: The CHIPS score identifies a subset of patients accounting for 22% of an intermediate risk population who are predicted to have an EFS <80%. Early augmentation of therapy may improve outcome for this cohort. After further validation of this approach in historical cohorts, future studies will evaluate the utility of the CHIPS in additional cohorts of newly diagnosed patients. Disclosures: No relevant conflicts of interest to declare.





Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2596-2603 ◽  
Author(s):  
Kara M. Kelly ◽  
Richard Sposto ◽  
Raymond Hutchinson ◽  
Vickie Massey ◽  
Kathleen McCarten ◽  
...  

AbstractDose-intensified treatment strategies for Hodgkin lymphoma (HL) have demonstrated improvements in cure but may increase risk for acute and long-term toxicities, particularly in children. The Children's Oncology Group assessed the feasibility of a dose-intensive regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in children with high-risk HL (stage IIB or IIIB with bulk disease, stage IV). Rapidity of response was assessed after 4 cycles of BEACOPP. Rapid responders received consolidation therapy with guidelines to reduce the risk of sex-specific long-term toxicities of therapy. Females received 4 cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) without involved field radiation therapy (IFRT). Males received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with IFRT. Slow responders received 4 cycles of BEACOPP and IFRT. Ninety-nine patients were enrolled. Myelosuppression was frequent. Rapid response was achieved by 74% of patients. Five-year event-free-survival is 94%, IFRT with median follow-up of 6.3 years. There were no disease progressions on study therapy. Secondary leukemias occurred in 2 patients. Overall survival is 97%. Early intensification followed by less intense response-based therapy for rapidly responding patients is an effective strategy for achieving high event-free survival in children with high-risk HL. This trial is registered at http://www.clinicaltrials.gov as #NCT00004010.



2014 ◽  
Vol 6 (1) ◽  
pp. e2014063 ◽  
Author(s):  
Eldad J Dann

Therapy of advanced Hodgkin lymphoma (HL) is a rapidly changing field due to a lot of currently emerging data. Treatment approaches are presently based on either the Kairos principle of giving aggressive therapy upfront and considering de-escalation of therapy if the interim PET/CT is negative or the Chronos principle of starting with ABVD followed by escalation of therapy for patients with positive interim PET/CT. The International Prognostic Score (IPS) is still valid for decision-making regarding the type of initial therapy, since patients with a high score do have an inferior progression free survival (PFS) with ABVD compared to those with a low score. Escalated BEACOPP administered upfront improves PFS; however, increase in the overall survival (OS) has not been confirmed yet, and this therapy is accompanied by elevated toxicity and fertility impairment. Completion of ongoing and currently initiated trials could elucidate multiple issues related to the management of HL patients.  



Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 215-215 ◽  
Author(s):  
Amanda R. Wedgwood ◽  
Michelle A. Fanale ◽  
Luis E. Fayad ◽  
Peter McLaughlin ◽  
Fredrick B. Hagemeister ◽  
...  

Abstract The use of rituximab in classical Hodgkin lymphoma (HL) has been proposed to have a therapeutic value by several mechanisms; to The malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) rarely survive outside their microenvironment of reactive B-cells, and therefore we hypothesized that depleting B-cells from HL microenvironment by rituximab may deprive HRS cells from critical survival and resistance factors and therefore improving the efficacy of chemotherapy, Rituximab may have a direct killing effect on HRS cells that express CD20, and recent data from Johns Hopkins Medical Center suggested that HRS stem cells are CD20+ cells. With this background, we evaluated the safety and efficacy the combination of rituximab and ABVD (R-ABVD) chemotherapy in newly diagnosed patients with classical HL. In addition, PET after 2–3 cycles of ABVD has been shown to confer poor prognosis and therefore proposed to guide future therapy. (Hutchings et al, Blood, 2006) reported a negative PET scan after two cycles of ABVD to be a good predictor of outcome with 96% 2-year progression free survival (PFS). Those with PET positive after 2 cycles had a 0% PFS at 2 years. Thus, we examined the effect of RABVD on early PET imaging and determined whether PET status remains predictive of treatment outcome in patients receiving RABVD. To date 70 newly diagnosed pts are enrolled, of whom 65 pts had at least 12 months of follow up and are evaluable for treatment response. Median age 28 years (Range; 18–72 years). Patients had stage II (50%), stage III (31%), stage IV (19%) disease. Using the IPS prognostic score model, 36 patients (55%) had a score of 2 or higher. With a median follow up of 32 months, the estimated event-free survival (EFS) is for the entire group is 85% and overall survival 98%. EFS for patients with IPS 0–1, 2, and &gt;2 are 95%, 76%, and 77%, respectively, suggesting that R-ABVD improved EFS in all IPS scores with the biggest impact seen in patients with IPS &gt; 2. 55 patients had PET after 2–3 cycles and were included in the predictive analysis of PET on treatment outcome. PET became negative in 43 patients (78%) after completing 2–3 cycles of RABVD and positive in the remaining 12 patients (22%). 5-year EFS for those with negative PET was 93% and 75% for those who remained PET positive (p=0.05). We conclude that in patients with classical HL, the addition of 6 weekly doses of rituximab to standard dose and schedule of ABVD chemotherapy is effective in terms of remission rate and remission duration irrespective of IPS category. Our data confirmed prior reports that patients who remain PET positive after 2–3 cycles have worse prognosis when compared to those that achieve PET negativity. However, the outcome for those who remained PET positive after 2–3 cycles of RABVD seems to be significantly better than what has been previously reported when using ABVD alone. A randomized trial comparing ABVD with RABVD is planned to confirm these observations.



2016 ◽  
Vol 57 (8) ◽  
pp. 1839-1847 ◽  
Author(s):  
Ljubomir R. Jakovic ◽  
Biljana S. Mihaljevic ◽  
Bosko M. Andjelic ◽  
Andrija D. Bogdanovic ◽  
Maja D. Perunicic Jovanovic ◽  
...  


2010 ◽  
Vol 51 (9) ◽  
pp. 1337-1343 ◽  
Author(s):  
J. J. Cerci ◽  
L. F. Pracchia ◽  
C. C. G. Linardi ◽  
F. A. Pitella ◽  
D. Delbeke ◽  
...  


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