scholarly journals Normalization of pre-ASCT, FDG-PET imaging with second-line, non–cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma

Blood ◽  
2012 ◽  
Vol 119 (7) ◽  
pp. 1665-1670 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Matt J. Matasar ◽  
Andrew D. Zelenetz ◽  
Stephen D. Nimer ◽  
John Gerecitano ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
Pet Scan ◽  
High Dose ◽  
Cell Transplant ◽  
18Fdg Pet ◽  
Fdg Pet Scan ◽  
Intent To Treat

Abstract We previously reported that remission duration < 1 year, extranodal disease, and B symptoms before salvage chemotherapy (SLT) can stratify relapsed or refractory Hodgkin lymphoma (HL) patients into favorable and unfavorable cohorts. In addition, pre-autologous stem cell transplant (ASCT) 18FDG-PET response to SLT predicts outcome. This phase 2 study uses both pre-SLT prognostic factors and post-SLT FDG-PET response in a risk-adapted approach to improve PFS after high-dose radio-chemotherapy (HDT) and ASCT. The first SLT uses 2 cycles of ICE in a standard or augmented dose (ICE/aICE), followed by restaging FDG-PET scan. Patients with a negative scan received a transplant. If the FDG-PET scan remained positive, patients received 4 biweekly doses of gemcitabine, vinorelbine, and liposomal doxorubicin. Patients without evidence of disease progression proceeded to HDT/ASCT; those with progressive disease were study failures. At a median follow-up of 51 months, EFS analyzed by intent to treat as well as for transplanted patients is 70% and 79%, respectively. Patients transplanted with negative FDG-PET, pre-HDT/ASCT after 1 or 2 SLT programs, had an EFS of > 80%, versus 28.6% for patients with a positive scan (P < .001). This prospective study provides evidence that the goal of SLT in patients with Hodgkin lymphoma should be a negative FDG-PET scan before HDT/ASCT. The study was registered at www.clinicaltrials.gov as NCT00255723.

scholarly journals Current strategies for salvage treatment for relapsed classical Hodgkin lymphoma

2017 ◽  
Vol 8 (10) ◽  
pp. 293-302 ◽  
Author(s):  
Liana Nikolaenko ◽  
Robert Chen ◽  
Alex F. Herrera
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Early Stage Disease ◽  
First Line Therapy

Hodgkin lymphoma (HL) is curable in 70–80% of patients with first-line therapy. However, relapses occur in a minority of patients with favorable early stage disease and are more frequent in patients with advanced HL. Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) for patients with chemotherapy-sensitive disease is a standard treatment sequence for relapsed or refractory (rel/ref) HL. Patients who achieve complete response prior to ASCT have better survival outcomes. The choice of salvage chemotherapy therapy is becoming increasingly difficult in the era of novel agents, as there are no randomized studies to guide the choice of a second-line regimen. In this article, we will review current salvage therapy options, including combination chemotherapy and novel-agent-based salvage regimens for rel/ref HL.

Prognostic Value of FDG-PET in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2090-2090
Author(s):  
Jakub Svoboda ◽  
Rebecca Elstrom ◽  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Arnold Berkowitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Fdg Pet ◽  
Salvage Chemotherapy ◽  
Pet Scan ◽  
High Dose ◽  
Fdg Pet Scan ◽  
Refractory Lymphoma

Abstract High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients (pts) with relapsed or primary refractory lymphoma that is responding to salvage chemotherapy. Limitations of ASCT include significant morbidity, cost, restriction of further treatment options, and frequent relapse of lymphoma. To define the ability of FDG-PET to predict clinical outcome after ASCT, we conducted a retrospective analysis of lymphoma pts in our institution who received salvage chemotherapy followed by ASCT for relapsed or primary refractory lymphoma between 1999 and 2005. We identified 47 lymphoma pts (19 with diffuse large B-cell, 18 with Hodgkin, 4 with mantle cell, 3 with follicular and 3 with other lymphomas) who had an FDG-PET scan after at least two cycles of salvage chemotherapy and prior to ASCT. Three pts were excluded from the analysis because their FDG-PET scan results were non-conclusive. The remaining 44 pts (median age 44 yrs, range: 19–65) were categorized into FDG-PET scan negative (26 pts) and positive (18 pts) groups. Each group was evaluated for event-free survival (EFS), which was defined as the interval between the date of the transplant to the date of relapse after complete remission (CR) or the date of progression for pts without CR or the date of death from any cause without a documented relapse. The overall median follow-up was 14 mo (range: 2–58). There were no statistically significant differences in the distribution of lymphoma subtypes between the two groups. In the FDG-PET negative group, the median EFS was 18 mo (range: 3–58) with 14 pts (54%) remaining in CR. In the FDG-PET positive group, the median EFS was 5 mo (range: 1.5–19) with only 1 pt (6%) remaining in CR. Comparison between the two groups confirmed that the difference in the median EFS was highly statistically significant (p<0.001). Additional data to determine the correlation of the FDG-PET with conventional CT scans will be presented. Our study suggests that a positive FDG-PET scan after salvage chemotherapy and prior to ASCT indicates an extremely poor chance of achieving a prolonged remission after ASCT. Clinical trials of new approaches should be investigated for pts with relapsed or primary refractory lymphoma that remains detectable by FDG-PET after salvage chemotherapy. Figure Figure

scholarly journals Autologous stem cell transplants - single center standpoints for lymphoma patients

2017 ◽  
Vol 70 (suppl. 1) ◽  
pp. 47-50
Author(s):  
Milena Todorovic-Balint ◽  
Bela Balint ◽  
Jelena Bila ◽  
Dragana Vujic ◽  
Bosko Andjelic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Stem Cell Transplant ◽  
Standard Condition ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Prognostic Features

Autologous stem cell transplant with high-dose chemotherapy is considered to be an effective treatment strategy for outcome improvement in lymphoma patients, especially those with refractory and relapsed disease. Despite the feasibility and efficacy of autologous stem cell transplant, patients with lymphoma still face the risk for relapse, mostly patients who have adverse prognostic features. Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant is recognized as the most effective strategy for relapsed or refractory Hodgkin lymphoma or aggressive non-Hodgkin lymphoma improving their response rate. First line therapy is ABVD (Hodgkin lymphoma patients), R-CHOP or R-CHOP-like regimens while salvage regimens such as DHAP, ESHAP, ICE represent the standard of care for relapsed/refractory lymphoma patients. Before autologous stem cell transplant, standard condition regimens are BEAM or CBV.

scholarly journals Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2887
Author(s):  
Timothy J Voorhees ◽  
Anne W Beaven
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
The United States ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Novel Agents ◽  
Cell Transplant ◽  
T Cell Therapy

Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.

High dose chemotherapy with autologous stem cell transplant for patients with transformed B-cell non-Hodgkin lymphoma in the rituximab era

2014 ◽  
Vol 55 (10) ◽  
pp. 2319-2327 ◽  
Author(s):  
Yngvild N. Blaker ◽  
Marianne B. Eide ◽  
Knut Liestøl ◽  
Grete F. Lauritzsen ◽  
Arne Kolstad ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Non Hodgkin Lymphoma

Early Pre/Post Fluoro-Deoxyglucose Positive Emission Tomography (PET) Does Not Predict Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation in Hodgkins Disease and Non-Hodgkins Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2180-2180
Author(s):  
Jeanne Palmer ◽  
Timothy Goggins ◽  
Gloria Broadwater ◽  
Nelson J. Chao ◽  
John Chute ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Fdg Pet ◽  
Pet Scan ◽  
Cell Transplant ◽  
Hodgkins Lymphoma ◽  
Radiology Reports ◽  
Fdg Pet Scan ◽  
Pet Scans

Abstract This study was designed to investigate the predictive value of early pre/post stem cell transplant (SCT) FDG-PET on outcomes in non hodgkins (NHL) or Hodgkins lymphoma (HL). We analyzed patients who received SCT for treatment of relapsed or refractory NHL or HL at Duke Medical Center between the years of 1996–2007. Patients who had either a FDG-PET scan following salvage chemo- or radio- therapy and within 14 weeks of transplantation (pre-PET)or a FDG PET scan within 6–14 weeks following transplantation (post-PET) were included in the analysis. PET was determined to be positive or negative based on chart review of radiology reports. Survival times are estimated using Kaplan- Meier method. Hazard ratios (HR) are from univariate Cox proportional hazards models. Overall survival (OS) was measured from the time of transplant until death, and for those patients still alive, it was censored at the last follow up date. Disease free survival (DFS) was measured from the time of transplant until first progression or death, whichever occurred first, and was censored at the date of last follow up for those alive without progression. A total of 102 patients were identified with PET in the appropriate time period. Median age was 48.5 (18–78); 71 patients had NHL, 31 patients had HL. Ninety-eight (96%) of the patients had chemosensitive disease, and had a documented PR (62) or CR (36) prior to transplant. The median DFS and OS of this population was 55 and 73 mo respectively. Median time to follow up was 38 mo (1.5 – 145 mo). Of the 75 pre-PET scans, 32 (43%) were positive; of the 78 post-PET scans, 22 (28%) were positive. At the time of this analysis, 28 (27%) of the patients had died from disease progression. There were 8 (10.6%) pre-PET, and 7 (9%) post- PET readings that were not clear. Our analysis revealed that neither pre-PET nor post-PET results were predictive of DFS (HR 1.73 p=0.16, HR 1.97 p = 0.052) or OS (HR 1.92 p=0.13; HR1.65 p=0.21). Further, for the patients who had measurable disease at the entry to SCT, post-PET was not predictive for DFS (HR 1.62, p=0.29) or OS (HR 1.59 p=0.35). Exclusion of unclear PET readings did not have any effect on these results. In subset analysis, post- PET did predict DFS in patients with NHL (HR 2.6 p=0.034). Our results suggest that early pre/post SCT PET analysis is not beneficial in this algorithm for predicting overall survival in these patients. Negative post-PET may predict DFS in patients with aggressive NHL, however, did not predict OS in this group. Our analysis indicates that other methods of determining risk of relapse and transplant outcome are needed.

EARLY Interim FDG-PET Scan in Localised Hodgkin Lymphoma: Evaluation of Practice in 5 French Centers

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4935-4935
Author(s):  
Olivier Fitoussi ◽  
Pauline Brice ◽  
Sandrine Hirt ◽  
Philippe Solal-Celigny ◽  
Marie-Sarah Dilhuydy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Early Stage ◽  
Dose Intensity ◽  
Pet Scan ◽  
Treatment Intensification ◽  
Term Survival ◽  
Early Stage Disease ◽  
Fdg Pet Scan ◽  
Pre Treatment

Abstract Background: Long-term survival from Hodgkin lymphoma (HL) in early-stage (I–II) patients is more than 85%. However, certain patients have a primary refractory disease with a worse evolution. Early interim FDG-PET scan performed after 2 courses of chemotherapy (PET-2) provides an early and accurate assessment of response and a correlation has been demonstrated between normalization of PET-2 and patient outcome. Aim: To evaluate the percentage of negative PET-2 in early-stage patients, and to seek clinical or biological factors predictive of positive PET-2. Methods: Sixty-five patients from five French centers with early-stage Hodgkin lymphoma received ABVD as firstline chemotherapy. PET-2 was performed 3 weeks after the second course of ABVD. Radiotherapy and changes in management according to FDG-PET scan result could be decided by the clinician. Evaluation was retrospective. Results: The median age was 36 years (range17–77). Thirty-nine patients were male. Seventy-three percent of patients were in unfavorable group according to EORTC criteria (one or more of the following criteria: age &gt; 50, systemic symptoms, elevated ESR &gt;50 mm, bulk disease and more than three lymph node areas involved). Fifty-seven patients had a pre-treatment FDGPET scan with a modification of staging in 6 cases. Initial staging according to CT scan or FDG-PET scan was as follows: IA: 5 patients, IB: no patient, IIA: 35 patients and IIB: 25 patients. Fifty-three patients (82%) had a negative PET-2 whereas 12 patients (18%) had a clearly positive PET-2. Among the 53 patients with negative PET-2, 47 patients underwent radiation therapy after completion of four courses of ABVD. Among the 12 patients with positive PET-2, treatment intensification (BEACOPP) occurred for 7 patients with a negative FDG-PET scan for 6 of them after two courses. For the 5 PET+ patients pursuing with ABVD: three had a negative FDG-PET scan and two had a positive FDGPET scan after four cycles of ABVD. At a median follow-up of 30 months, 6 patients relapsed early after the end of the treatment (2 in the negative PET-2 group and 4 in the positive PET-2 group). Out of the 7 patients of the positive PET-2 group receiving an increase dose intensity of chemotherapy (BEACOPP), 3 of them relapsed. The 59 other patients did not presented any failure or relapse at the present time. Conclusion: We showed in this series that negative PET-2 is obtained in 82% of patients with early stage disease. These results are similar to those expected in the EORTC H10 trial which evaluates PET-2 guided treatment adaptation and expect about 85–90% of negative PET-2. This retrospective study augurs that positive TEP2 is a pejorative prognostic factor and the utilisation of the BEACOPP treatment in these population remains to define. Prospective studies, like H10 EORTC trial are warranted to confirm these results and find predictive factors for a positive PET-2.

Normalization of FDG-PET Pre-ASCT with Additional Non-Cross Resistant Chemotherapy Improves EFS in Patients with Relapsed and Primary Refractory Hodgkin Lymphoma-Memorial Sloan Kettering Protocol 04-047

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 775-775 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Stephen D. Nimer ◽  
Andrew D. Zelenetz ◽  
Paul A. Hamlin ◽  
Steven M. Horwitz ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Standard Dose ◽  
High Dose Chemotherapy ◽  
Pet Scan ◽  
High Dose ◽  
Remission Duration ◽  
Fdg Pet Scan ◽  
Extranodal Disease ◽  
Involved Field

Abstract We have reported that outcome of transplant-eligible patients (pts) with relapsed and primary refractory HL is determined by three pre-second-line chemotherapy (ST) risk factors (RF): remission duration of <1 yr., extranodal disease and B symptoms. In addition, normalization of FDG-PET prior to ASCT is the most important factor predicting favorable EFS. We now report the preliminary results of an ongoing phase II risk-adapted study where HL pts receive the following: Favorable risk (0–1 RF) - one cycle of standard dose ifosfamide, carboplatin and etoposide (ICE) ST followed by one cycle of augmented ICE; unfavorable risk (2-RF)- 2 cycles of augmented ICE. All pts then underwent a restaging FDG-PET and the results determined the next treatment. Pts with a negative FDG-PET went directly to HDT/ASCT; however if the FDG-PET was still positive, pts received an additional four biweekly cycles of gemcitabine (1000 mg/m2), vinorelbine (20 mg/m2) and liposomal doxorubicin (15 mg/m2) (GVD) followed by repeat FDG-PET scan; pts without evidence of progression then received HDT/ASCT. Preceding high-dose chemotherapy and ASCT, patients that were radiation therapy-naive received involved field radiotherapy (IFRT) followed by total lymphoid irradiation. Selected previously irradiated patients received only IFRT. Sixty-two pts are evaluable; median follow-up of surviving pts is 30 months; median age was 35. Forty-eight pts had a remission duration of < 1 yr. of those, 28 had primary refractory disease; 28 had extranodal disease and 11 had B symptoms. All patients had previously failed doxorubicin-based chemotherapy; 18 had received prior radiation; of those, 13 failed in the radiation field. Following first ST chemotherapy with ICE, 3 pts progressed, while 37 pts normalized their FDG-PET scan and currently 31 of these pts are event-free. Twenty-five pts with an improving CT scan after ICE still had a persistently positive FDG-PET; they received the second ST with GVD. Of these, 13 pts normalized their FDG-PET scan and 11 are eventfree; the remaining 12 pts had persistently abnormal FDG-PET scan or progressed; only 4 of them are event-free. There was no difference in outcome between the pts who had normal FDG-PET after ICE (pre-ASCT) and those who achieved a negative FDG-PET scan because of the additional ST with GVD. Both of these cohorts had a statistically significant improvement in EFS compared to pts with a persistently positive FDG-PET. In total 46/62 (65%) pts on this program are currently event-free. One pt died from sepsis. Conclusion: For pts with relapsed and primary refractory HL our evolving strategy is to administer ST until normalization of FDG-PET is achieved prior to HDT/ASCT. Figure Figure

Impact on Pulmonary Function of Pre-Transplant Radiotherapy in Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant (ASCT).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3279-3279
Author(s):  
Christy Stotler ◽  
Paul Elson ◽  
Brian Bolwell ◽  
Matt Kalaycio ◽  
Brad Pohlman ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Cleveland Clinic ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Post Transplant ◽  
Significant Difference

Abstract For patients (pts) with Hodgkin lymphoma (HL) undergoing initial treatment with chemotherapy, often in conjunction with radiation therapy (RT), the rate of relapse ranges from 10 to 15 % in favorable prognosis stage I-II disease to 30 to 40 % in advanced disease. Patients with poor prognosis after first relapse, those with a second relapse, and pts with progressive disease are candidates for high dose chemotherapy followed by ASCT. A noted risk factor in HL patients following ASCT is development of pulmonary toxicity. The effect of prior conditioning regimens and RT on lung function has been implicated. Scant data is available regarding whether proximity of RT to time of transplant increases the risk for development of subsequent pulmonary toxicity. To address this question we retrospectively reviewed 172 sequential HL patients with pre-and post-transplant pulmonary function data who underwent ASCT at the Cleveland Clinic between 1985 and 2008 using a prospectively maintained, IRB approved, database. Bu/Cy/VP was the preparative regimen in 83% of pts (n=142), BCNU/Cy/VP in 13% of pts (n=22), and Melphalan in 4% of pts (n=7). The post-transplant change in pulmonary function (percent predicted DLCO and FEV1) in pts who received RT prior to ASCT was compared to those who did not receive RT. The timing of the RT was also examined. Statistical analysis was performed using the Wilcoxon rank sum test. 67 pts (39%) received pre-transplant RT at a median of 14.1 months prior to ASCT; 10 pts received RT ≤6 months prior to ASCT, 50 pts received RT >6 months before, and timing was unknown for seven pts. Overall, pts experienced a median 3.2% decline in DLCO (range 53.7% decline to 137.5% improvement) and a 2.9% decline in FEV1 (range 71.8% decline to 33.3% improvement) following transplant. The decline in DLCO and/or FEV1 was significant (>25%) in 16% of patients. The change in DLCO post-ASCT was not significantly different between pts who did or did not receive pre-transplant RT (median declines of 2.7% vs. 3.7%, respectively, p=1.0). There was, however, a significant difference with respect to FEV1. Pts who had prior RT experienced a median 6.4% decline in FEV1 following ASCT compared to a median 1.1% decline in pts who did not have prior RT (p=.03). The proportion of pts in whom the decline in FEV1 was significant however was similar in the two groups (7% vs. 6% respectively, p=1.0). Pts treated with pre-transplant RT within 6 months of ASCT tended to have greater declines in both DLCO and FEV1 following ASCT than patients not treated with RT (median declines: DLCO: 8.8% versus 0%; FEV1: 7.7% versus 4.8%, respectively); however the differences were not significant (p=.25 and .98, respectively). Conclusions: Pts treated with RT prior to ASCT experience a greater decline in FEV1 post-transplant than RT-naïve patients. The decline, however, is not generally of clinical significance, and the proportion of pts with clinically significant impairment of pulmonary function is similar in the two groups.

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