PET Scan Predicts Survival After Transplant for Relapsed Diffuse Large B-Cell Lymphoma
PET Scan Predicts Survival After Transplant for Relapsed Diffuse Large B-Cell Lymphoma
Abstract & Commentary
Andrew Artz, MD, Division of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationships relevant to this field of study.
Synopsis: High-dose chemotherapy and autologous hematopoietic stem cell transplant (ASCT) is standard therapy for relapsed or refractory diffuse large B-cell lymphoma after salvage chemotherapy. In this retrospective study of 39 patients with diffuse large B-cell lymphoma (DLCL) who had undergone ASCT, the authors assessed outcomes based on post-salvage pre-ASCT PET imaging. PET scans were positive in 17 (44%) and negative in 22 (56%) after salvage. A negative PET scan predicted for less relapse and better three-year OS at 81%, compared to 39% for PET-positive patients. Results are excellent for patients achieving PET negativity prior to ASCT; the optimal approach for PET-positive patients remains undefined.
Source: Dickinson M, et al. Improved survival for relapsed diffuse large B-cell lymphoma is predicted by a negative pre-transplant FDG-PET scan following salvage chemotherapy. Br. J. Haematol. 2010;150:39-45.
High-dose chemotherapy, followed by reinfusion of autologous hematopoietic stem cells (ASCT), represents the standard of care for patients relapsing from diffuse large B-cell lymphoma (DLCL) with chemosensistive disease.1 Chemosensitivity to treatment after relapse remains a critical determinant to outcome.2 More precise determination of disease responsiveness may be obtained employing 18fluoro-2-deoxy-d-glucose positron-emission tomography (FDG-PET). Lack of PET response early after CHOP chemotherapy predicts for poor outcome.3 The authors evaluated the utility of PET scanning for relapsed DLCL prior to ASCT.
In this retrospective review from two institutions, they identified 39 patients who received an ASCT between 2002 and 2007 for relapsed or refractory DLCL, and a PET scan was performed prior to ASCT. Salvage chemotherapy consisted of numerous regimens, most commonly ifosfamide, carboplatin, and etoposide (ICE) with rituximab (RICE). ASCT used peripheral blood stem cells and a variety of conditioning regimens, including BCNU, etoposide, ara-c and melphalan (BEAM) (n = 15), cyclophosphamide, BCNU, etoposide (CBV), busulphan/melphalan (bu/mel) (n = 7), and TBI based regimens (n =4).
PET scans were positive prior to ASCT in 17 (44%), whereas 22 (56%) had negative PET scans. There were no deaths documented related to transplant complications. Overall survival (OS) and progression-free survival (PFS) was 67% and 64% at three years, respectively. Relapse occurred in 11/17 with positive PET scans, compared to 4/22 with negative PET scans (HR = 5.3, 95% CI 1.8-15.5), despite greater use of post-ASCT radiation in the PET positive cohort. OS was 39% for PET-positive patients, compared to 81% for PET-negative patients (p = 0·01). For patients with primary refractory DLCL (n = 13), irrespective of PET results, three-year OS was 46%. Of these, relapse occurred in five of seven with positive PET scans and three of six with negative PET scans. Thus, for PET-negative patients, relapse primarily occurred in those entering salvage with primary refractory disease.
In a multivariate model including relapsed vs. refractory disease and PET result, a negative PET scan was associated with longer OS (p = 0·04), whereas relapsed compared to refractory did not reach statistical significance (p = 0·06). Age-adjusted IPI was missing in many patients and, thus, not included in these models. Twenty-eight patients underwent CT scanning in addition to PET or PET/CT scanning for restaging. All six patients with a confirmed CR by CT scanning showed a negative PET scan, and none of these patients relapsed. For those who did not achieve CR (i.e., residual mass by CT), PET results were 75% specific for (95% CI: 53%-90%) and 73% sensitive (95% CI: 45%-91%) for relapse.
Commentary
Autologous hematopoietic stem cell transplantation (ASCT) remains the standard of care for relapsed or refractory DLCL. Disease sensitivity to salvage chemotherapy strongly predicts for outcome, and most transplant centers require chemosensitive disease (PR or CR) to salvage. With the advent of routine PET imaging, incorporation of the results should inform prognostication for potential ASCT recipients.
As expected and suggested by other publications,4,5 patients with a negative PET scan at the completion of salvage chemotherapy, but prior to ASCT, fared quite well. Only 4/22 (18%) with negative PET scans relapsed. In contrast, 65% of those with positive PET scans suffered relapse, even though many received additional therapy, such as post-ASCT radiation. OS at three years was achieved by 81% of those having negative PET scans vs. 39% in those with positive imaging (p = 0.01). Although a negative PET scan resulted in inferior results after ASCT, OS at three years of 39% in such a poor prognosis group suggests ASCT may still provide a benefit for select patients in this cohort. The largest limitation of this retrospective study design relates to this study being derived from patients who underwent ASCT. It is quite possible, if not likely, that patients having positive PET and/or CT scans after salvage chemotherapy did not proceed to ASCT. As a result, OS and relapse, particularly for PET-positive DLCL after salvage chemotherapy, may be considerably worse than described. Criteria for PET positivity also remain controversial and may be subject to greater variation in community practice.
These results confirm the value of PET negativity after salvage chemotherapy for relapsed or refractory DLCL prior to ASCT. Whether PET or PET/CT can substitute for standard CT imaging in this setting requires further evaluation. For PET positive patients, in addition to ASCT, consideration should be given to clinical trials, novel therapies, or allogeneic SCT.
References
1. Philip T, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995;333:1540-1545.
2. Kewalramani T, et al. High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: An intention-to-treat analysis. Blood. 2009;96:2399-2404.
3. Kostakoglu L, et al. FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease. Cancer. 2006;107:2678-2687.
4. Johnston PB, et al. Positron emission tomography using F-18 fluorodeoxyglucose pre- and post-autologous stem cell transplant in non-Hodgkin's lymphoma. Bone Marrow Transplant. 2008;41:919-925.
5. Schot BW, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood. 2007;109: 486-491.
High-dose chemotherapy and autologous hematopoietic stem cell transplant (ASCT) is standard therapy for relapsed or refractory diffuse large B-cell lymphoma after salvage chemotherapy. In this retrospective study of 39 patients with diffuse large B-cell lymphoma (DLCL) who had undergone ASCT, the authors assessed outcomes based on post-salvage pre-ASCT PET imaging. PET scans were positive in 17 (44%) and negative in 22 (56%) after salvage. A negative PET scan predicted for less relapse and better three-year OS at 81%, compared to 39% for PET-positive patients. Results are excellent for patients achieving PET negativity prior to ASCT; the optimal approach for PET-positive patients remains undefined.Subscribe Now for Access
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