Risk Adapted Treatment in Childhood Hodgkin's Lymphoma: Outcome and Changing Epidemiologic Features in 25 Years

Abstract IntroductionThe survival of children with Hodgkin lymphoma have increased significantly raising the issue of decreasing late effects by using risk adapted treatment. Hodgkin lymphoma has different epidemiologic features in developed and developing countries. In this study the epidemiologic, clinical characteristics and outcome of children with Hodgkin disease treated with a risk adapted treatment over a 25 year period are evaluated. MethodsThis retrospective study evaluates the clinical characteristics and outcome of 122 children treated with the same institutional risk-adapted protocol in the Istanbul University, Oncology Institute between 1991-2016. Clinical staging was done according to Ann-Arbor staging, all patients had biopsy confirmation and the WHO histopathological classification was used. Imaging (ultrasound, CT/MRI and/or PET-CT since 2004) was done in all patients. Bone marrow aspiration and biopsy was done for all with B symptoms or risk group 2 and 3. Risk group 1 (clinical group IA/B and IIA) recieved 2 courses of ABVD (adriamycin 25 mg/m2, bleomycin 10 U/m2, vinblastin 6 mg/m2 and dacarbazine 375 mg/m2 , day 1 and 15) chemotherapy, risk group 2 (stage IIB and IIIA) 4 courses of ABVD, risk group 3 patients (IIIB,IVA/B) 6 courses of COPP/ABV (cyclophosphamide 600 mg/m2, vincristine 1.4 mg/m2 on day 1, procarbazine 100 mg/m2 day1-7, prednisolone 40 mg/m2 day1-14; adriamycine 35 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2 day 8) chemotherapy, each course administered every 28 days. All patients recieved involved field radiotherapy 15-25 Gy adjusted to age (15 Gy for < 5, 20 Gy for 5-10, 25 Gy for >10 years old), + 5 Gy for bulky disease and/or partial response to chemotherapy. Results There were 83 males and 39 females (M/F: 2.1) with a median age of 10 (2-18) years. The most frequent histological subtypes were mixed cellularity (41%) and nodular sclerosing (41%). The most common involved site was the neck (cervical and supraclavicular lymph nodes) (%85). The median follow up period was 6 1/12 years (1-25 years). The 5 year event free survival and survival were 82% and 97% for all patients; they were 86% and 97% for risk 1 (48 patients), 80% and 96% for risk 2 (29 patients), 79% and 97% for risk 3 (45 patients) . B symptoms were present in 46%; %54 were staged as I-II; 46% as stage III-IV. When classified according to two time periods: before and after 2000, the median age increased [9 (2-17) vs 11 (3-18) years], M/F ratio decreased [2.7 (36/13) vs 1.8 (47/26)] and the most common histological subtype were mixed cellularity (51%) vs nodular sclerosing (49%) respectively. The 5 year event free survival and survival were 79% and 95% before 2000 and 83,5% and 98% after 2000 respectively. Ebstein Barr Virus-Latent membrane Protein (EBV-LMP1) was found to be positive by immunohistochemistry in all tumor samples of 21 patients analyzed, all were treated before 2000. During follow-up no clinically evident cardiotoxicity or pulmonary toxicity has been observed. Three patients developed secondary tumors (Langerhans cell histiocytosis, schwannoma, non-Hodgkin's lymphoma). ConclusionThe epidemiologic features of HL is related to socioeconomic status. In our cohort, the oberved change in epidemiologic features within 25 years, such as the increase in median age, decrease in the M/F ratio and increase in nodular sclerosing subtype, is thought to be related to the socioeconomic development. A high survival rate has been achieved with the institutional risk-adapted protocol for all risk groups. The use of risk adapted protocols providing efficient and least toxic treatment is very important in pediatric Hodgkin lymphoma. Disclosures No relevant conflicts of interest to declare.

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Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽

10.1182/blood.v84.9.3122.3122 ◽

1994 ◽

Vol 84 (9) ◽

pp. 3122-3133 ◽

Cited By ~ 414

Author(s):

A Reiter ◽

M Schrappe ◽

WD Ludwig ◽

W Hiddemann ◽

S Sauter ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

Multicenter Trial ◽

Low Risk ◽

Event Free Survival ◽

Free Survival ◽

Risk Patients ◽

To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

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PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽

10.1182/blood.v116.21.1772.1772 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1772-1772

Author(s):

Santiago Pavlovsky ◽

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Miguel Pavlovsky ◽

Virginia Prates ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Progressive Disease ◽

Cell Transplant ◽

Advanced Stage ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study

Journal of Clinical Oncology ◽

10.1200/jco.20.03096 ◽

2021 ◽

pp. JCO.20.03096

Author(s):

Huyong Zheng ◽

Hui Jiang ◽

Shaoyan Hu ◽

Ning Liao ◽

Diying Shen ◽

...

Keyword(s):

High Risk ◽

Pediatric Patients ◽

Risk Group ◽

High Risk Group ◽

Event Free Survival ◽

Free Survival ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Standard Risk

PURPOSE Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

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Minimal Residual Disease by Flow Cytometry in Children with Acute Lymphoblastic Leukemia. Single-Center Experience

Blood ◽

10.1182/blood.v118.21.4238.4238 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4238-4238

Author(s):

Marcela Eugenia Soria ◽

Marcela Ema Gutierrez ◽

Maria Isabel Gaillard ◽

Maria Cores ◽

Gimena Gil ◽

...

Keyword(s):

Flow Cytometry ◽

High Risk ◽

Residual Disease ◽

Risk Group ◽

High Risk Group ◽

Event Free Survival ◽

Free Survival ◽

Wbc Count ◽

Minimal Residual

Abstract Abstract 4238 Introduction: Minimal residual disease (MRD) allows detection of blasts in patients in morphologically complete remission. Detection of MRD in patients with ALL is an independent risk factor associated with lower event-free survival (EFS). Objectives: 1) Evaluate MRD in bone marrowaspirateby flow cytometry at days 15 and 33 of induction in children with ALL. 2) Determine MRD association with hematologic features. 3) To correlate MRD association with overall survival (OS) and event-free survival (EFS). Design and Statistical Analysis: Descriptive, retrospective study. Univariate analysis was performed by T- test for continuous varibles and byχ2or Fisher tests for categorical variables. Survival was estimated with Kaplan Meier method. Regression multiple was used for multivariate analysis. p values < 0.05 were deemed as statistically significant. SPSS 15.0 program was used for the analyses. Patients: From January 2006 to December 2009, 84 patients with newly diagnosed ALL, aged 1 –18 years, were admitted at our institution. They were treated according to ALLIC / BFM / GATLA 2002 protocol. Immunophenotypic studies were performed by standard Four-color flow cytometry (FC) using FACSCalibur BD cytometer, MDR follow up panels were tailored depending on aberrant finding at diagnosis. 300.000–500.000 events were acquired using the CellQuest Pro and Paint -a-gate software for data analysis. MDR status has been defined as positive if at least 30–50 clustered events displaying leukemia –associated immunophenotypic characteristics (0,01%). Results: The mean age at diagnosis was 7.7 years (r: 2.1–18). Mean follow-up 33.9 months (r: 1–66). 38% were female. Immunophenotype: Pro B 5%, common B 87%, Pre B 2%, and T 6%. Good response to prednisone was achieved by 92% of patients. With regard to risk groups, the distribution was: 28% standard, 55% intermediate and 17% high. MRD at day 15 was evaluable in 66 patients (78%), being positive in 35 of them (45%). MRD at day 33 was evaluable in 75 patients (89%), being positive in 10 (12%). Conclusion: Positive MRD at day 15 was associated with: increased WBC count at diagnosis, high-risk group, higher relapse rate, lower EFS and OS. Otherwise, positive MRD at day 33 was associated: increased WBC count at diagnosis, T immunophenotype, poor response to prednisone, high risk group, lower EFS and OS. Our data indicate that positive MRD at days 15 and 33 result an independent variable of poor prognosis in children with ALL. Disclosures: No relevant conflicts of interest to declare.

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Progression of Aortic Stenosis and Long-term Follow-Up in Women

Clinical Cardiology and Cardiovascular Interventions ◽

10.31579/2641-0419/147 ◽

2021 ◽

Vol 4 (8) ◽

pp. 01-08

Author(s):

Ezra Amsterdam

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Rapid Progression ◽

Aortic Valve Area ◽

Event Free Survival ◽

Free Survival ◽

Entire Cohort ◽

Rapid Progressors ◽

Group 2

Data on the rate of progression of aortic stenosis (AS) in women are limited. We retrospectively studied 95 female patients (age 75 ± 13 yrs) with aortic valve area (AVA) <2.0 cm2 (mild AS 1.5-1.9 cm2, moderate AS 1.0-1.4 cm2, severe AS <1.0 cm2). All patients underwent serial transthoracic echocardiography. We determined annual AVA decrease (rate of AS progression) by 3 approaches, each of which was applied to the entire cohort: 1) as a single group; 2) in the 3 subgroups of mild, moderate and severe AS; and 3) in the rapid and slower progressors. Study endpoints were aortic valve replacement (AVR) and all-cause mortality. The mean duration of follow-up was 4.5 ± 2.9 years. Mean rate of reduction in AVA for the total study group was 0.14 ± 0.16 cm2/yr and was directly related to presence of hypertension and baseline AVA, and inversely related to follow-up duration (all p<0.05). The annualized decrease in AVA for each of the subgroups of mild, moderate and severe AS at baseline was 0.21±0.31 cm2, 0.13±0.11 cm2, 0.11±0.09 cm2, respectively (p<0.0001). Rapid progression of AS (decrease in AVA ≥0.20 cm2/yr) occurred in 21% of patients (n=20) and was associated with baseline hypertension (p=0.03) and inversely related to follow-up duration (p=0.0007). Rapid progressors had shorter follow-up than slower progressors (20 vs. 42 mos, p=0.002). Event-free survival with end-points of death (n=65) or surgical/transcatheter AVR (n=24) at 1, 3, and 5 years, respectively, was 93%, 66% and 40% for mild AS; 96%, 72% and 48% for moderate AS; and 93%, 38% and 24% for severe AS. Thus, event-free survival at 5 years in patients with baseline severe AS was approximately half that of patients with AS of mild or moderate severity. In addition, event-free survival at 1 year in slower progressors was 92% and in rapid progressors was 70%.

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Left ventricular non-compaction cardiomyopathy: additional predictors of life-threatening events for selecting patients for cardioverter-defibrillator implantation

EP Europace ◽

10.1093/europace/euab116.365 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

N Rineiska ◽

S Komissarova ◽

O Krasko ◽

I Haidzel

Keyword(s):

Survival Rate ◽

High Risk ◽

Myocardial Fibrosis ◽

Risk Group ◽

Left Ventricular ◽

Event Free Survival ◽

Free Survival ◽

Risk Patients ◽

Life Threatening

Abstract Funding Acknowledgements Type of funding sources: None. The aim of the study is to determine predictors of life-threatening arrhythmic events in order to identify high-risk patients requiring ICD/CRT-D implantation. Methods. The study included 155 patients with left ventricular non-compaction cardiomyopathy (NCСM), 59 (38.1%) women, 96 (61.9%) men, and a median age of 39 (28; 51) years. In addition to the standard examination, cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) was performed. The median follow-up was 36 months (6; 152). Endpoints of the study included life-threatening arrhythmic events (sustained VT/VF) requiring device implantation (ICD/CRT-D). Results. The most frequent types of arrhythmia were ventricular premature beats (VPB) >500 per day – in 64 (41.3%) pts, nonsustained ventricular tachycardia (VT) was observed in 54 (34.8%) pts, sustained VT – in 15 (9.7%) pts and permanent atrial fibrillation (AF) with episodes of nonsustained VT – in 34 (21.9%) pts. Syncope was recorded in 17 (11%) pts. Symptoms of NYHA FC III CHF were found in 28 (18.1%) pts. According to EchoCG data, the median LV ejection fraction (LVEF) was 44% (34; 54). According to LGE-CMR, 72 (46.8%) pts showed areas of myocardial fibrosis; the median volume of myocardial fibrosis was 13.2% (0.6; 58.5). During the follow-up period, life-threatening arrhythmic events (sustained VT/VF) developed in 15 pts, among which ICD – 8 and CRT-D – 7 were implanted as part of the secondary prevention of sudden cardiac death (SCD). The 3-year event-free survival rate was 88 ± 14%. In multivariate analysis, independent factors associated with the risk of life-threatening events requiring ICD/CRT-D implantation are the following characteristics: the presence of syncope (HR 12.5; 95% CI 3.9–39.7, p < 0.001), the presence of nonsustained VT (HR 11.8; 95% CI 1.5–95.1, p < 0.021) and the percentage of fibrosis volume ≥30% (HR 3.23; 95% CI 1.01–10.4, p < 0.048). Risk groups of life-threatening events were stratified based on multi-factor analysis. The three-year event-free survival rate of the high-risk group was 77.8 ± 5.8%, the low-risk group had no adverse events during the entire follow-up period, and the three-year event-free survival rate was 100%. Conclusion. The developed model of risk stratification of life-threatening events allows identifying high-risk patients for timely preventive measures.

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Lymphoblastic lymphomas in children: A single-center experience from Serbia

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1608413l ◽

2016 ◽

Vol 144 (7-8) ◽

pp. 413-417

Author(s):

Jelena Lazic ◽

Dragana Janic ◽

Nada Krstovski ◽

Predrag Rodic ◽

Goran Milosevic ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Survival Rates ◽

Event Free Survival ◽

Treatment Protocols ◽

Free Survival ◽

Single Center Experience ◽

Non Hodgkin Lymphoma ◽

Good Treatment Outcome ◽

Male Patients

Introduction. Intensive treatment protocols used for non-Hodgkin lymphoma in children lead to eventfree survival rates ranging from 80% to 90%. However, the results are less successful in developing countries. Lymphoblastic lymphoma (LBL) is the second most frequent type of lymphoma in children, contributing with about one third to all non-Hodgkin lymphoma in childhood. Objective. The aim of the study was to evaluate the results of LBL treatment in University Children?s Hospital (UCH), Belgrade. Methods. A retrospective analysis of patient records at UCH from 1997 to 2015 was carried out in patients aged 0-18 years, in whom the diagnosis of LBL had been established. Twenty-two children were included in the analysis. Results. Mean age at diagnosis was 10 years, with preponderance of male patients. All patients were treated according to Berlin-Frankfurt-M?nster-based chemotherapy protocols. With median follow-up of 91.5 months, five-year probability of event-free survival was 79.5% for all patients, while overall survival was 81.8%. Conclusion. Our results, although slightly inferior to those of leading international groups, reflect a good treatment outcome in our patients.

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Rituximab + ABVD Improves Event-Free Survival (EFS) in Patients with Classical Hodgkin Lymphoma in All International Prognostic Score (IPS) Groups and in Patients Who Have PET Positive Disease after 2–3 Cycles of Therapy.

Blood ◽

10.1182/blood.v110.11.215.215 ◽

2007 ◽

Vol 110 (11) ◽

pp. 215-215 ◽

Cited By ~ 9

Author(s):

Amanda R. Wedgwood ◽

Michelle A. Fanale ◽

Luis E. Fayad ◽

Peter McLaughlin ◽

Fredrick B. Hagemeister ◽

...

Keyword(s):

Treatment Outcome ◽

B Cells ◽

Hodgkin Lymphoma ◽

Prognostic Score ◽

Newly Diagnosed ◽

Classical Hodgkin Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Abvd Chemotherapy

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 >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 > 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.

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Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽

10.1182/blood.v84.9.3122.bloodjournal8493122 ◽

1994 ◽

Vol 84 (9) ◽

pp. 3122-3133 ◽

Cited By ~ 15

Author(s):

A Reiter ◽

M Schrappe ◽

WD Ludwig ◽

W Hiddemann ◽

S Sauter ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

Multicenter Trial ◽

Low Risk ◽

Event Free Survival ◽

Free Survival ◽

Risk Patients ◽

To Receive

In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

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Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽

10.32895/ump.mpr.3.3.1 ◽

2019 ◽

Vol 3 (3) ◽

pp. 1-6

Author(s):

Truc Phan ◽

Tram Huynh ◽

Tuan Q. Tran ◽

Dung Co ◽

Khoi M. Tran

Keyword(s):

Elderly Patients ◽

Hodgkin Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

The Elderly ◽

Free Survival ◽

Non Hodgkin Lymphoma ◽

Common Sign ◽

Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

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