Outcomes of Eam Conditioned Autologous Haematopoietic Stem Cell Transplantation for Lymphoma. A Matched Pairs Retrospective Single Centre Study Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3088-3088
Author(s):  
Justin Ching Ting Loke ◽  
Janice Ward ◽  
Prem Mahendra ◽  
Sridhar Chaganti ◽  
Ram Malladi

Abstract Abstract 3088 Background: High dose chemotherapy followed by autologous stem cell rescue is superior to salvage chemotherapy alone in relapsed Hodgkin's Lymphoma (HL) and Non-Hodgkin's lymphoma (NHL). A commonly used regimen is BEAM (BCNU, Etoposide, Cytarabine and Melphalan). Unfortunately, BCNU is associated with potentially lethal pulmonary interstitial toxicity, in a dose dependent manner. Therefore, it is often omitted in conditioning regimens for patients who have pre-existing impaired lung function. We aimed to determine the outcomes of patients given this EAM (Etoposide, Cytarabine, Melphalan) schedule in our centre. Method: At our unit, from 2000–2010, 338 patients had been transplanted with BEAM conditioning and 23 patients with an EAM regimen. BEAM chemotherapy involved cumulative doses of BCNU at 300 mg/m2, etoposide at 800 mg/m2, cytarabine at 1600 mg/m2 and melphalan at 140 mg/m2. The EAM regimen was the same, except for the omission of BCNU. We wanted to compare overall survival, event free survival and transplant related mortality between the two groups of patients. A matched-pair analysis based on age and sex on a 1:1 basis was conducted. Survival rates were estimated by the Kaplan-Meier method. Differences between the survival distributions were compared with the log-rank test. Results: 23 patients transplanted with an EAM regimen was matched with an equal number transplanted with a BEAM conditioning regimen. The median age was 53 in both groups. The median follow-up for patients alive was 3.2 years. Further baseline characteristics of the two groups are described in table 1. Other than a slight predominance of more advanced disease in the BEAM cohort, the two groups were evenly matched. Survival estimates were statistically significantly poorer for the EAM group compared to the BEAM group. The median overall survival for the EAM cohort was 29 months compared to 77 months (p=0.03) for the matched BEAM cohort. The median event free survival for the EAM cohort was 11 months compared to 63 months (p=0.02) for the BEAM cohort. The 100 day transplant related mortality was 8.7% for both cohorts. During the follow-up period 11 patients died of disease related causes in the EAM group compared to 6 in the BEAM group. Conclusion: Despite the prevalence of pre-existing lung disease in the EAM group of patients, the conditioning was reasonably well tolerated. Our analysis suggests that patient transplanted with an EAM regimen had an inferior survival outcome to patients treated with the standard BEAM regimen. This data provides evidence for the importance of BCNU in lymphoma control; consideration should be given to a reduction in BCNU dosage, rather than simple omission, for patients with borderline lung function results. Collaboration with other centres is warranted to determine if this experience with EAM is replicated elsewhere. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4208-4208
Author(s):  
Alessandro de Moura Almeida ◽  
Erika Maria Macedo ◽  
Claudia Mac Donald Bley ◽  
Fabio R. Kerbauy ◽  
Paulo Vidal Campregher ◽  
...  

Abstract Abstract 4208 Introduction: Despite preventive and therapeutic antiviral medication cytomegalovirus (CMV) infection is still a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (SCT). Only limited data on CMV infection and disease are available in autologous SCT recipients. Previous studies have demonstrated that the probability of CMV infection is nearly 60% in seropositive patients and 23% in seronegative patients undergoing autologous SCT, but its impact in mortality is unclear. Methods: We retrospectively reviewed the medical records of 101 patients undergoing autologous SCT at Hospital Israelita Albert Einstein from January, 2005 to July, 2012. CMV infection was defined as a quantitative real time PCR assay showing greater than 165 copies and/or positive CMV pp65 antigenemia assay. Lymphocyte count was registered at 15th day after SCT and lymphopenia was defined as an absolute lymphocytes count (ALC) < 500 at that time point. Overall survival (OS) was estimated from the time of transplant until death, with surviving patients censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value <0.10 in the univariate analysis. CMV infection was analyzed as a time-dependent covariate, considering the time to CMV infection. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: The majority of patients were male (62.4%) and the median age was 58 years old (range: 3–76). Peripheral stem cell harvest was the main source of cells (92%). A positive serological CMV status was found in 93.75% of patients. Most common indications for autologous SCT were multiple myeloma (34%), non-Hodgkin's lymphoma (40%) and Hodgkin's lymphoma (6%). After a median follow-up of 2 years, the OS for the whole cohort was 61% (95% confidence interval [CI] 48–72%). CMV infection post SCT was seen in 26% of patients. In the univariate analysis, development of CMV infection and presence of D15 lymphopenia were associated with a higher mortality (CMV infection-hazard ratio [HR] 3.32 [95%IC 1.61–6.84]; p= 0.001; D15 lymphopenia- HR 2.37 [95% IC 1.11–5.05]; p= 0.024). Patients who developed CMV infection in the setting of D15 lymphopenia had the worse outcome (2-years OS 19%; 95% CI 9–43%; figure 1). D15 lymphopenia was not associated with a higher rates of CMV infection (p=0.41). In Cox multivariate analysis, lower overall survival was demonstrated in female patients (HR= 2.23, 95%IC 1.08–4.58; p= 0.029), in the presence of D15 lymphopenia (HR= 2.56, 95%IC 1.19–5.51; p= 0.016) and CMV infection (HR: 3.33, 95% IC1.61–46.86; p= 0.001). Conclusion: CMV infection post-autologous SCT is associated with a decreased survival, and in the concomitant presence of D15 lymphopenia appears to indicate a subgroup of patients with very poor outcome. It is possible that CMV infection does not lead directly to increased mortality, but is rather a surrogate marker of decreased immune function post-ASCT. Future studies should prospectively evaluate the incidence and prognostic impact of CMV infection post-ASCT and correlate with markers of immune recovery. Disclosures: No relevant conflicts of interest to declare.


2015 ◽  
Vol 6 (4) ◽  
pp. 13-18
Author(s):  
Svetlana Aleksandrovna Kulyova ◽  
Andrei Petrovich Karitsky ◽  
Svetlana Viacheslavovna Ivanova

Background. Calculation of relative tumor burden in Hodgkin’s lymphoma patients is the simplest and significant parameter which can be used in daily clinical practice as a risk factor. The aim of study was the assessment of influence of relative tumor burden on the late results of a disease. Material and methods. This research included data on 126 patients with Hodgkin’s lymphoma aged from 0 till 18 years (middle age of 11 years), treated risk-adapted treatment according to the DAL-HD and SPBLH-05. Boys was 70, girls - 56 (a ratio 1,25 : 1). Fifty-eight patients (46 %) are stratified in favorable risk group, 50 (39,7 %) - in intermediate risk group, and 50 (39,7 %) are included in unfavorable risk group. Results. Overall survival at 5 years was 93 % (range 91-95 %), event-free survival - 88 % (85-91 %). The average relative tumor burden was 129,4 cm3/m2 (7-609,7 cm3/m2). When carrying out ROC-analysis value of 122,7 cm3/m2 (р ˂ 0,0001) appeared the critical parameter, which worsen the prognosis of a disease. Overall survival in a patients cohort with this volume was 69,6 %, with the volume less than 122,7 cm3/m2 overall survival was 97,2 % (р = 0,00002). Conclusions. The relative tumor burden is the parameter which is significantly reducing survival rates in children with Hodgkin’s lymphoma. Opinion on interrelation of clinical and laboratory parameters with “sarkoma’s saturation” or tumor volume as end result of immunological frustration, it is represented the most perspective direction of studying of Hodgkin’s lymphoma.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 672-672 ◽  
Author(s):  
A. R. Zander ◽  
N. Kroeger ◽  
C. Schmoor ◽  
W. Krueger ◽  
V. Moebus ◽  
...  

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m2), Cyclophosphamide (600 mg/m2) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m2), Thiotepa (150 mg/m2) and Mitoxantrone (10 mg/m2) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m2), Methotrexate (40 mg/m2) and Fluoruracil (600 mg/m2) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.


2008 ◽  
Vol 23 (4) ◽  
pp. 207-213
Author(s):  
W. Gui ◽  
T. Wang ◽  
J. Wang ◽  
L. Wang ◽  
J. He ◽  
...  

We aimed to evaluate the prognostic value of the combination of three serum tumor markers (LDH, β2-M and CA 125) in patients with non-Hodgkin's lymphoma (NHL). Clinical and pathological variables including the levels of these markers were measured in 415 NHL patients. Statistical analysis showed that increased levels of all three markers were associated with stage, B symptoms, effusions, bone marrow involvement, and International Prognostic Index (IPI) in NHL patients (p<0.05). Overall survival and event-free survival rates were associated not only with LDH but also with β2-M and CA125 (p<0.001). Response to treatment and overall survival rates were different in three groups with elevated LDH; in particular, the combination of three or two elevated markers seemed to identify a group of patients at higher risk of treatment failure and/or relapse than the group with a high LDH level only. Furthermore, multiple Cox regression analysis showed that IPI score complemented by the additional serum markers β2-M and CA125 was a better prognosticator of overall and event-free survival than LDH alone. This result suggests that if the combination of three elevated serum tumor markers is included as a parameter in the IPI instead of LDH alone, the prognostic value of IPI can be improved.


Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2540-2544 ◽  
Author(s):  
Catherine Sebban ◽  
Nicolas Mounier ◽  
Nicole Brousse ◽  
Coralie Belanger ◽  
Pauline Brice ◽  
...  

AbstractThe purpose of this study is to compare our standard chemotherapy regimen (CHVP [cyclophosphamide, doxorubicin, teniposide, and prednisone]) plus interferon with 4 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by high-dose therapy with autologous stem cell transplantation (ASCT) in treatment-naive patients with advanced follicular lymphoma. Four hundred one patients were included from July 1994 to March 2001: 209 received 12 cycles of CHVP plus interferon α for 18 months (CHVP-I arm) and 192 received 4 cycles of CHOP followed by high-dose therapy (HDT) with total body irradiation and ASCT (CHOP-HDT arm). Overall response rates were similar in both groups (79% and 78% after induction chemotherapy, respectively). One hundred thirty-one of the 150 patients eligible for HDT underwent transplantation (87%). Intent-to-treat analysis after a median follow-up of 7.5 years showed that there was no difference between the 2 arms for overall survival (P = .53) or event-free survival (P = .11). Patients with a complete response at the end of the induction therapy had a statistically longer event-free survival and overall survival (P = .02 and < .001, respectively). After long-term follow-up, our study showed that there was no statistically significant benefit in favor of first-line high-dose therapy in patients with follicular lymphoma. High-dose therapy should be reserved for relapsing patients.


2015 ◽  
Vol 6 (4) ◽  
pp. 5-12
Author(s):  
Margarita Borisovna Belogurova ◽  
Elmira Gosmanovna Boichenko ◽  
Svetlana Aleksandrovna Kulyova

The statistics (incidence, mortality, survival) characterizing a problem and the oncological care to children with malignant tumors in St. Petersburg are presented in the article. It is proved that intensification in the therapeutic regimens according to immunohistochemical features, age, extending of tumor significantly raised survival rates, having approached them to the world. The five-year survival of children treated in the 90th of the last century in St. Petersburg, was 60,9 %, at the beginning of the 2000th increase of survival to 69,3 % with approach to European survival (71,8 %) is noted. Improvement of indicators of survival, first of all, should be explained with progress in therapy of the most widespread localizations - leukemias and central nervous system tumors. Thanks to an intensification of treatment it was succeeded to improve considerably results of treatment of children with acute leukemia: the survival from 10-15 % in the 70-80th reached 80 %. Traditionally good results were observed at Hodgkin’s lymphoma: the 5-year overall survival was 94% with event-free survival of 87 %. Using of the European protocol for treatment of Wilm’s tumor (SIOP 93-01) increased survival of children with a unilateral tumor to 94,4 % at the overall survival more than 80 %. Improvement of overall survival in children was influenced also by introduction in practice protocols of BFM (Berlin-Frankfurt-Münster) for treatment non-Hodgkin’s lymphoma thanks to what 5-year event-free survival increased from 30 to 81 %. Now the perspective in children’s oncology are development of molecular and genetic diagnostics with search the germ mutations at a hereditary cancer syndrome, definition of a range of somatic mutations in genes at sporadic malignant tumors at children.


2019 ◽  
Vol 37 (2) ◽  
pp. 144-152 ◽  
Author(s):  
Clémentine Sarkozy ◽  
Matthew J. Maurer ◽  
Brian K. Link ◽  
Hervé Ghesquieres ◽  
Emmanuelle Nicolas ◽  
...  

Purpose Although the life expectancy of patients with follicular lymphoma (FL) has increased, little is known of their causes of death (CODs) in the rituximab era. Patients and Methods We pooled two cohorts of newly diagnosed patients with FL grade 1-3A. Patients were enrolled between 2001 and 2013 in two French referral institutions (N = 734; median follow-up 89 months) and 2002 and 2012 in the University of Iowa and Mayo Clinic Specialized Program of Research Excellence (SPORE; N = 920; median follow-up 84 months). COD was classified as being a result of lymphoma, other malignancy, treatment related, or all other causes. Results Ten-year overall survival was comparable in the French (80%) and US (77%) cohorts. We were able to classify COD in 248 (88%) of 283 decedents. In the overall cohort, lymphoma was the most common COD, with a cumulative incidence of 10.3% at 10 years, followed by treatment-related mortality (3.0%), other malignancy (2.9%), other causes (2.2%), and unknown (3.0%). The 10-year cumulative incidence of death as a result of lymphoma or treatment was higher than death as a result of all other causes for each age group (including patients ≥ 70 years of age at diagnosis [25.4% v 16.6%]) Follicular Lymphoma International Prognostic Index score 3 to 5 (27.4% v 5.2%), but not Follicular Lymphoma International Prognostic Index score 0 to 1 (4.0% v 3.7%); for patients who failed to achieve event-free survival within 24 months from diagnosis (36.1% v 7.0%), but not for patients who achieved event-free survival within 24 months of diagnosis (6.7% v 5.7%); and for patients with a history of transformed FL (45.9% v 4.7%), but not among patients without (8.1% v 6.2%). Overall, 77 of 140 deaths as a result of lymphoma occurred in patients whose FL transformed after diagnosis. Conclusion Despite the improvement in overall survival in patients with FL in the rituximab era, their leading COD remains lymphoma, especially after disease transformation. Treatment-related mortality also represents a concern, which supports the need for less-toxic therapies.


2006 ◽  
Vol 24 (36) ◽  
pp. 5735-5741 ◽  
Author(s):  
Lionel M.L. Chow ◽  
Paul C. Nathan ◽  
David C. Hodgson ◽  
Derek Jenkin ◽  
Sheila Weitzman ◽  
...  

Purpose Reduced-intensity protocols for pediatric Hodgkin's lymphoma are aimed at preserving excellent relapse-free survival while decreasing the incidence of late effects. Patients and Methods We retrospectively reviewed the outcome of 123 children treated consecutively for Hodgkin's lymphoma at a single institution. Patients with stages I-IIIB disease received three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/ doxorubicin, bleomycin, and vinblastine (ABV) followed by 15 Gy of extended-field irradiation, while those with stage IV disease were treated with six to eight cycles of MOPP/ABV chemotherapy with or without radiotherapy. Results At a median follow-up of 8.5 years (range, 1.4 to 15.5 years), the estimated 10-year overall survival and event-free survival are 94% (SE, 2.2%) and 88% (SE, 3.1%) respectively. There have been 12 treatment failures and six disease-related deaths. A very large mediastinal mass (≥ 50% of the maximal thoracic diameter) was associated with a 10-year event-free survival of 50% (SE, 14%) compared with 91% (SE, 4.0%) for smaller masses (P < .001). Late cardiopulmonary toxicity is largely absent, and the incidence of hypothyroidism is 14%. There have been no cases of secondary leukemia and four secondary solid malignancies observed to date. Conclusion MOPP/ABV and low-dose, extended-field radiotherapy is an effective treatment for pediatric Hodgkin's lymphoma. With median follow-up of 8.5 years, late cardiopulmonary effects and secondary malignancies from this treatment regimen are infrequent. Continued longitudinal observations, particularly for breast cancer in female patients and gonadotoxicity, will determine whether the goal of decreasing treatment-related complications while maintaining excellent survival has been achieved.


Medicina ◽  
2009 ◽  
Vol 45 (8) ◽  
pp. 615 ◽  
Author(s):  
Eduardas Aleknavičius ◽  
Konstantinas Valuckas ◽  
Birutė Aleknavičienė ◽  
Laura Norkienė ◽  
Giedrė Smailytė

During last decades, there are strengthening attitudes to optimize the treatment of Hodgkin’s lymphoma considering prognostic groups and risk factors. Based on the data of Vilnius University Clinics, a retrospective study was carried out, and treatment methods and outcomes of the patients treated during 1999– 2004 were analyzed. Medical histories of 114 patients younger than 60 years were reviewed. Median age was 28 years. In 83% of cases, classic nodular sclerotic Hodgkin’s lymphoma was diagnosed. Advanced-, intermediate-, and early-stage disease was diagnosed in 55%, 38%, and 7% of cases, respectively. The patients with early-stage disease underwent four ABVD chemotherapy courses; 88% of them underwent radiotherapy afterwards. The patients with intermediate-stage disease underwent 4–6 courses of ABVD or in minor cases (12% of patients with intermediate-stage disease) – 4 standard BEACOPP chemotherapy courses. After this treatment, 88% of patients with intermediate-stage disease underwent radiotherapy. Patients with advanced-stage disease underwent 8 escalate (44%) or standard BEACOPP (29%) chemotherapy courses. More than half of these patients (71%) underwent radiotherapy after chemotherapy. Patient follow-up median was 65 months. One hundred seven patients (94%) after primary treatment achieved complete remission, in 7 patients (6%) primary progression was observed, 12 patients (11%) relapsed, and 8 patients died. Overall survival and event-free survival in patients with early-stage disease was 100%. Overall survival in patients with early/intermediate- and advanced-stage disease was 95.1% and 84.0%, respectively. Event-free survival in patients with early/intermediate- and advanced-stage disease was 91.7% and 76.2%, respectively. In the groups of intermediate- and advanced-stage disease, the results of treatment were worse in the subgroup, which underwent extended-field radiotherapy (P<0.05). Overall survival in the group of patients with advanced-stage disease was the best who underwent ABVD scheme, but the event-free survival (70.6%) and disease-free survival (81.3%) in ABVD subgroup were worse compared to BEACOPP subgroup. According to our results, there was no statistically significant difference in survival of patients with advanced-stage disease who underwent or did not radiotherapy (P>0.05).


2008 ◽  
Vol 26 (8) ◽  
pp. 1282-1288 ◽  
Author(s):  
Monika L. Metzger ◽  
Sharon M. Castellino ◽  
Melissa M. Hudson ◽  
Shesh N. Rai ◽  
Sue C. Kaste ◽  
...  

Purpose Some cooperative groups have found a survival disadvantage in black children with various childhood cancers. We examine the effects of race on clinical outcomes among children with Hodgkin's lymphoma (HL) treated with contemporary therapy at a tertiary care children's hospital. Patients and Methods Retrospective analysis of 327 children and adolescents diagnosed with HL between 1990 and 2005. Patients were treated with risk-directed multimodal therapy regardless of race, ethnicity, or ability to pay. Event-free and overall survival rates were compared for black and white children. Clinical characteristics, socioeconomic factors, and biologic features were analyzed for prognosis of treatment failure. Results The 262 white and 65 black patients did not differ significantly in presenting features, clinical characteristics, or enrollment in a clinical trial. More black patients (71% v 45%) resided in poor counties (P < .001). While black and white children were equally likely to have progressive disease or early relapse, black children were 3.7 times (95% CI, 1.7 to 8.0) more likely to relapse 12 months or more after diagnosis. The 5-year event-free survival was 71% ± 6.1% (SE) for black and 84% ± 2.4% for white children (P = .01). However, the 5-year survival rate did not differ between white and black children (94.4% v 94.7%). While black race and low hemoglobin concentration were independent predictors of treatment failure, only low hemoglobin concentration independently predicted poor survival. Conclusion Black children with Hodgkin's lymphoma have lower event-free survival than white children, but both populations have the same 5-year overall survival.


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