The Prognostic Value of FDG PET/CT Prior to Autologous Stem Cell Transplant in Mantle Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3113-3113
Author(s):  
Jonathon B. Cohen ◽  
Nathan Hall ◽  
Amy S. Ruppert ◽  
Jeffrey A. Jones ◽  
Pierluigi Porcu ◽  
...  

Abstract Abstract 3113 Background: Pre-transplantation FDG-PET/CT (PET/CT) has been associated with progression-free survival (PFS) and overall survival (OS) in patients (pts) with relapsed Hodgkin's and diffuse large B-cell lymphoma (Spaepan, Blood.102 :53-59, 2003). However, no data exist regarding the role of PET/CT pre-transplant in pts with mantle cell lymphoma (MCL). We performed a retrospective analysis of pts with MCL and available pre-transplant PET/CT to evaluate the association of pre-transplant PET/CT findings with PFS and OS. Methods: PET/CT was reviewed by a single radiologist according to International Harmonization Committee (IHC) criteria with mediastinal blood pool as the referenced background activity and also utilizing liver blood pool. Bone marrow (BM) uptake was not utilized in the PET/CT response assessment. Associations between PET/CT positivity and clinical characteristics were performed using Fisher's Exact and Wilcoxon rank sum tests. PFS curves were constructed from date of transplant until date of relapse or death by the Kaplan-Meier method and evaluated by the log-rank test. Univariable proportional hazards models described the relationship between clinical variables and PFS. Results: Twenty-nine pts with PET/CT prior to autologous stem cell transplant were included. Median age was 60 (range 37–73), and 86% were male. Median MIPI was 5.9 (range 4.9–7.0), with 36%, 40%, and 24% of pts classified as low (< 5.7), intermediate (5.7–6.2), or high risk (> 6.2), respectively. At diagnosis, 93% of pts had BM involvement, 56% had splenomegaly, and 27% had bulky adenopathy ≥ 5cm. Sixty-nine percent of pts were induced with RCHOP and methotrexate (RCHOP+M, Damon, JCO 27 :6101–6108); other therapies included RCHOP (n=4), RHyperCVAD (n=2), bortezomib (n=2), and REPOCH (n=1). Sixty-six percent, 21%, and 14% of pts received 2, 3–5, or 6 induction cycles prior to transplant, respectively. Conditioning regimens were BEAM (59%) and BEC (41%) and 90% of pts underwent transplant in first remission. Median time to transplant from diagnosis was 5.4 months (range 3.4–82). With a median follow up of 18 months (range 0.7–43), estimated median PFS is 42 months (95% CI 15–45). There have been 7 relapses (4 RCHOP, 1 RCHOP+M, 1 bortezomib, 1 REPOCH) and 5 deaths (disease progression, n=3, and pneumonia, n=2). Seventeen pts (59%) had a negative PET/CT prior to transplant, with identical results using mediastinal or liver blood pool. In 19, 6, and 4 pts respectively receiving 2, 3–5, and 6 cycles of induction therapy, 58%, 50%, and 75% were PET/CT negative prior to transplant. PET/CT positive pts received RCHOP+M (n=10), RCHOP (n=1), and bortezomib (n=1), Compared to PET/CT negative pts, PET/CT positive pts were younger (median age 55 v. 62, p=0.04) with lower MIPI (p=0.05). There was no significant association of bulky adenopathy (p=0.09), induction with RCHOP+M (p=0.23), or number of induction cycles (p=0.87) with PET/CT findings. 5 pts had a positive pre-transplant BM biopsy, of which 2 were BM negative by PET/CT. BM positivity on pre-transplant PET/CT was observed in 14 pts with only 3 also positive by BM biopsy. Median PFS was 45 months (95% CI 13–45) for PET/CT negative pts and 33 months (95% CI 3–33) in PET/CT positive pts (Figure 1; p=0.03). At this time, 4 of 17 PET/CT negative pts have progressed or died compared to 5 of 12 PET/CT positive pts. Of the 5 deaths experienced thus far, 4 have occurred in PET/CT positive pts. Presence of bulky adenopathy ≥ 5cm was also associated with a worse PFS (p=0.01), but MIPI (p=0.31) and age (p=0.61) were not. Conclusions: PET/CT associates with PFS after autologous stem cell transplantation in MCL (p=0.03). However, additional follow-up is needed to see if this association between PET/CT positivity and early relapse in MCL persists. In addition, as the majority of pts had 2 cycles of induction therapy with RCHOP+M, the impact of treatment regimen and number of cycles is difficult to assess in this series. Interestingly, neither age nor MIPI were associated with PFS from transplant, perhaps indicating that clinical characteristics at diagnosis are less important in pts that achieve a complete response by IHC criteria prior to transplant. Prospective investigation with centrally reviewed PET/CT scans compared with standard CT is required to determine the predictive role of pre-transplant PET/CT in MCL. Disclosures: No relevant conflicts of interest to declare.

2017 ◽  
Vol 23 (3) ◽  
pp. S265-S266
Author(s):  
Irl Brian Greenwell ◽  
Kelly Valla ◽  
Sarah Caulfield ◽  
Jeffrey M. Switchenko ◽  
Ashley Staton ◽  
...  

2017 ◽  
Vol 53 (3) ◽  
pp. 347-351
Author(s):  
Umberto Falcone ◽  
Haiyan Jiang ◽  
Shaheena Bashir ◽  
Richard Tsang ◽  
Vishal Kukreti ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2446-2446 ◽  
Author(s):  
Jorge Enrique Romaguera ◽  
Luis E. Fayad ◽  
Michael Wang ◽  
Fernando Cabanillas ◽  
Fredrick Hagemeister ◽  
...  

Abstract Mantle cell lymphoma (MCL) has a poor prognosis. Relapsed/refractory patients must respond to salvage chemotherapy in order to receive potentially curative stem cell transplantation (SCT). A salvage regimen with higher rate of response will offer the patient a better chance of survival. We have previously reported the results of R-HCVAD alternating with R-M-A in frontline therapy of MCL (Blood, 104:40a, 2004, (Abstract #128). The current trial looked at relapsed/refractory MCL patients treated also with R-HCVAD alternating with R-M-A. Since August 2001, the trial has accrued 24 out of a planned number of 41 patients of whom 21 are evaluable for response and survival. Median age was 63 years (range 45–78) and male:female ratio was 5:1. Three patients had received previous R-HCVAD alternating with R-M-A and three patients had failed an autologous stem cell transplant. Immediate therapy prior to the study for the 21 patients included R-HCVAD/SCT (1), CHOPw/wo rituximab (8 patients), cyclophosphamide, vincristine and rituximab (1), fludarabine (1), fludarabine, mitoxantrone, dexamethasone and rituximab (2), fludarabine and cyclophosphamide (1), radiotherapy (2), gemcitabine, mitoxantrone and dexamathasone (1) ifosfamide, carboplatin, etoposide and rituximab (1), Velcade (1), gemcitabine (1), and rituximab (1). The median number of prior regimens was one (range 1–6). Responses to the previous treatment included complete response (CR; 8 patients, 38%), partial response (PR; 6 patients, 29%), and no response or progression (7 patients, 33%). Results of the trial are as follows: Median number of cycles received = 4 (range 1–7), with an overall response rate (ORR) of 95% (43% CR/Cru; 52% PR). 5/5 patients who had progressed through the previous treatment responded (1CR, 4 PR), and 2/2 patients who had no change to the prior therapy responded (2 PR’s). We evaluated 12 cases whose response in our trial was classified as PR and found that in 4 of them it was the best response achieved but another 4 were referred to transplant while the tumor was still responding and in another case treatment was still ongoing. In 3 cases toxicity precluded continuation of therapy. Five (24%) of the patients were consolidated with non-myeloablative allogeneic stem cell transplantation. Sixteen were not transplanted for the following reasons: age (2 patients), lack of donor (5), Progressive disease (2), patient refusal (4), physician’s choice (1), waiting for match (1), and lost to follow up (1). Toxicity after 81 cycles included neutropenic fever (14%), grade 4 neutropenia (58%) and grade 4 thrombocytopenia (53%). The were no deaths due to toxicity. With a median follow-up of 21 months range 5–45 months), the median failure-free survival is 18 months as compared to a median FFS of 9 months response duration with the previous therapy, with no plateau in the curve. Patients who underwent stem cell transplant were censored at the time of transplant. The high response rates achieved R-HCVAD alternating with R-M-A makes this regimen an excellent choice for induction therapy prior to stem cell transplantation.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4491-4491
Author(s):  
Daniel C McFarland ◽  
Parameswaran Venugopal ◽  
Yan Li ◽  
Youping Deng ◽  
Stephanie A. Gregory

Abstract Abstract 4491 Background: Mantle cell lymphoma is typically considered to be aggressive and incurable. About 15% of these patients have an indolent course. MCL demonstrates the aggressive features of a rapidly progressive neoplasm but with the negative consequences of an indolent lymphoma, namely incurability and frequent relapses. The median overall survival (OS) was reported at 3–4 years when MCL was first described in the 1990's. OS has since increased substantially and this is thought to be secondary to more aggressive initial therapy and improvement in supportive care. In many parts of the world, autologous stem cell transplant (ASCT) is incorporated in the front line therapy for MCL patients with good performance status. However, improvement in survival has not deemed MCL a curable disease. Concern for treatment-related morbidity seen with aggressive therapy in an incurable disease has led some centers to practice a more conservative approach. The purpose of our study was to compare patient characteristics and the overall survival of patients treated aggressively with ASCT versus conservatively with either conventional chemotherapy or no treatment at a single institution. Methods: 52 cases of confirmed mantle cell lymphoma diagnosed at Rush University Medical Center between January 2000 and November 2010 were studied. Demographic, clinical and treatment data were collected and reviewed. The Social Security Death Index and hospital records were used to assess survival. Comparative survival analysis was performed based on treatment strategies including the following: no treatment (watch and wait), chemotherapy, ASCT at any time during course of treatment. None of these patients had an allogeneic stem cell transplant. Results: 43 of the 52 cases met all inclusion criteria and had complete diagnostic and treatment data. The no-treatment group consisted of 5 cases with a median age of 59 years. The chemotherapy group included 23 cases with a median age of 68 years. The most common initial therapy was RCHOP in 14 cases, followed by various other regimens (i.e. bortezomib + rituximab, bendamustine + rituximab) in 7 cases and HyperCVAD in 2 cases. The ASCT group included 15 cases with a median age of 61 years. Pre-transplant chemotherapy was RCHOP in 4 cases, HyperCVAD in 5 cases and other regimens in 6 cases. The comparative survival analysis for the three treatment groups was not statistically significant (p=0.496) and the estimated 3 year OS was 100% for the no treatment group, 74% for the chemotherapy group and 85% for the ASCT group. The estimated 5 year OS was 100% for the no treatment group, 66% for the chemotherapy group and 68% for the ASCT group. There were no cases of allogeneic stem cell transplants. Conclusions: Our review of MCL cases treated at a single institution supports a role for conservative treatment approaches to this disease entity. This can avoid the potential long term morbidity from ASCT in a subgroup of patients while still keeping the modality of therapy as an option for them at relapse. The incidence of indolent MCL requiring no treatment was 12% which is consistent with those seen in other studies. Further research is necessary to guide treatment decisions for MCL patients whose disease characteristics are intermediate between aggressive and indolent. Disclosures: Gregory: Genentech:.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4202-4202
Author(s):  
Ajay K. Nooka ◽  
Jonathan L. Kaufman ◽  
A. Tuba Karagulle Kendi ◽  
Yan Li ◽  
Chikaodili O Obidike ◽  
...  

Abstract Background: In the context of improved novel therapeutic anti-myeloma regimens using combinations of antibodies and other small molecules, measuring the efficacy of therapy is an ongoing challenge. Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC), polymerase chain reaction (ASO-PCR), next-generation sequencing are sensitive tests that are becoming more significant as improved therapies result in deeper responses, however challenges remain, such as standardizing these testing methods. 18F Fluorodeoxglucose Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that can provide essential information in diagnosis and management of MM. PET/CT has high sensitivity (80-90%) and specificity (80-100%) to detect MM lesions. PET/CT also has a recently acknowledged role in prognostic information. Standardized uptake value maximum (SUVmax) is a widely used PET/CT parameter for assessment of therapy response in a variety of cancers. Recent publication by Zamagni et al showed that in addition to the presence of three or more focal lesions, a maximum standardized uptake value (SUVmax) of over 4.2 and presence of extramedullary disease were negative prognostic factors. Our aim in this study was to evaluate the prognostic role of PET/CT in MM patients post ASCT at day 100 restaging. Methods: We have identified 130 myeloma patients that underwent autologous stem cell transplant (ASCT) from 09/2014 until 04/2015. Along with their hematologic restaging post-ASCT for response assessment per International Myeloma Working Group (IMWG) criteria, patients also underwent PET/CT for MRD assessment. After excluding 3 patients that underwent tandem transplants, and one patient that received stem cell boost, 102 patients were evaluable for the current analysis (24 patients did not undergo PET/CTs). We have done an exploratory analysis with previously described SUVmax cut off of <2.0 (Waheed S) and <4.2 (Zamagni E). Results: The median age of the patients that underwent ASCT was 64 years (range: 38-76 years). 77 pts (75%) received melphalan 200 mg/m2, 22 pts (22%) received melphalan 140 mg/m2, 2 pts received melphalan+bortezomib and 1 pt received BEAM regimen as conditioning regimen. Median time from day 0 to response assessment is 98 days (range: 55-189 days). Hematological restaging shows that 89% of patients achieved ≥VGPR (SCR: 46% and CR: 11%). 13 pts did not have prior lytic lesions while 89% had lytic lesions (one lesion: 4%, two lesions: 2% and multiple (≥3): 82%). PET/CT negativity was achieved among 63% of the patients. At SUV cut off of <2.0 and <4.2, PET/CT negativity was achieved among 64% of the patients and 83% of the patients respectively. Taking the patients that have achieved SCR, for the same cut offs, PET/CT negativity rates were 59% and 76% respectively (Table 1). Conclusions: Negative PET/CT rates post-ASCT are in accordance with previously published studies. With taking SUVmax as sole criteria for assessing MRD negativity, false positive PET/CT results will continue to remain a challenge. Although SUVmax is the most widely used PET/CT parameter, it has limitations. There are other PET/CT parameters mean or peak standardized uptake values (SUVmean, SUVpeak); metabolic tumor volume (MTV); total lesion glycolysis (TLG); standardized added metabolic activity (SAM); and, normalized standardized added metabolic activity (NSAM) used in clinical practice and research. These PET/CT parameters may have role as prognostic imaging probes in MM patients post ASCT. With longer follow up to assess PFS and OS, we can evaluate the prognostic impact of using PET/CT as MRD measure. Table 1. PET parameters and hematological responses Response Response rates PET positive PET negative PET positive (≥SUV 2.0) PET negative (<SUV 2.0) PET positive (≥SUV 4.2) PET negative (<SUV 4.2) SCR 46 19 27 19 27 11 35 CR 11 7 4 6 5 3 8 VGPR 34 9 25 9 25 3 31 PR 10 2 8 2 8 0 10 PD 1 1 0 1 0 1 0 ≥CR 57 26 31 25 32 14 43 ≥VGPR 91 35 56 34 57 17 74 Disclosures Nooka: Onyx Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Gleason:Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Lonial:Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5427-5427 ◽  
Author(s):  
Seah H. Lim ◽  
William V. Esler ◽  
David Beggs ◽  
Colleen Burris ◽  
Yana Zhang ◽  
...  

Abstract Conventional chemotherapy is non-curative for mantle cell lymphoma (MCL). Although the addition of Rituxan has improved the outcome of these patients, many patients still relapsed and died of their disease. High dose chemotherapy followed by autologous stem cell transplant (ASCT) has been investigated but produced conflicting results, ranging from no demonstrable benefit to a 2-year event-free survival (EFS) of 77%. A recent randomized study compared ASCT with interferon-a maintenance and showed benefits in both the EFS and overall survival for patients in the ASCT study arm. The conflicting results are probably related to the use of different chemotherapeutic agents as conditioning regimens for the transplant and also to different post-transplant therapy. In this study, we have chosen to induce patients with advanced MCL with R-CHOP and consolidate these patients with high dose single agent melphalan, a cytotoxic that has not been previously tested as a single agent in MCL. Since most patients relapsed within the first two years after transplant, low dose maintenance Rituxan therapy is given three-monthly during the first 2 years after ASCT. Following consent from the patients, 8 consecutive patients with advanced Stage III or IV MCL were treated. There were 5 male and 3 female, with a median age of 642 years (range 46–72 years). One patient had Stage III and the other 7 Stage IV diseases. All eight patients received remission + 2 courses of R-CHOP as induction chemotherapy. Autologous stem cells were harvested upon recovery from the last course of R-CHOP and ASCT carried out within 6 weeks from the last course of R-CHOP. High dose intravenous melphalan (200 mg/m2) was administered followed, 24 hours afterward, by the infusion of a minimum of 2 × 106/kg of CD34+ autologous stem cells. Rituxan maintenance therapy was initiated at a dose of 375 mg/m2 given as a single infusion once every three months starting Day +100. As of August 2006, with a median follow-up of 45.5 months from diagnosis (range 10–57 months) and 39 months from ASCT (range 4–52 months), seven patients are alive lymphoma-free, as defined by clinical and PET-CT examination. One patient died in CR of a myocardial infarction. Adverse effects were as expected from the high dose melphalan, except that delayed immunoglobulin reconstitution, as reported previously, was observed in all eight patients. Four of these hypogammaglobulinemic patients had recurrent infections (three with recurrent respiratory tract infection and one with a chronic diarrhea that was Vancomycin sensitive) and two required monthly intravenous immunoglobulin replacement. The result presented here is, therefore, extremely encouraging for a group of patients who normally have a very poor clinical outcome and warrants confirmation in larger multicenter study.


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