-
1.
Radiation Therapy Can Be Safely Incorporated into Pretransplantation Treatment Regimens for Patients with Multiple Myeloma
Damron, E. P., Qazilbash, M. H., Fang, P. Q., Wu, S. Y., Dabaja, B. S., Rondon, G., Hosing, C., Champlin, R. E., Bashir, Q., Shpall, E. J., et al
Transplantation and cellular therapy. 2023;29(1):37.e1-37.e7
Abstract
Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 10(6) CD34(+)/kg PBPCs (range, .5 to 54.8× 10(6) CD34(+)/kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 10(6) CD34(+)/kg PBPCs, and 166 (83%) collected >5.0 × 10(6) CD34(+)/kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.
-
2.
Radiation Therapy for Young Children Treated With High-Dose Chemotherapy and Autologous Stem Cell Transplant for Primary Brain Tumors
Milgrom, S. A., Koo, J., Foreman, N., Liu, A. K., Campbell, K., Dorris, K., Green, A. L., Dahl, N., Donson, A. M., Vibhakar, R., et al
Advances in radiation oncology. 2022;7(4):100945
Abstract
PURPOSE : The role of peri-transplant radiation therapy (RT) in children with primary brain tumors is unclear. We characterized our institutional practice patterns and patient outcomes. METHODS AND MATERIALS The cohort included all patients treated with high-dose chemotherapy and autologous stem cell transplant for primary brain tumors at our institution from 2011 to 2017. Rates of local control, progression-free survival, overall survival, and radiation-associated injury were assessed. RESULTS Of the 37 eligible patients, 29 (78%) received peri-transplant RT. Patients treated with RT were more likely to have metastatic (P = .0121) and incompletely resected (P = .056) disease. Of those treated with RT, 13 (45%) received craniospinal irradiation (CSI) and 16 (55%) received focal RT. The median CSI dose was 23.4 Gy (interquartile range [IQR], 18-36 Gy; boost: median, 54 Gy [IQR, 53.7-55.8 Gy]) and focal RT dose was 50.4 Gy [IQR, 50.4-54.5 Gy]). Compared with the focal RT group, patients treated with CSI were older (P = .0499) and more likely to have metastatic disease (P = .0004). For the complete cohort, 2-year local control was 82% (95% confidence interval [CI], 70%-96%), progression-free survival 63% (95% CI, 49%-81%), and overall survival 65% (95% CI, 51%-82%). These rates did not differ significantly between patients treated with and without peri-transplant RT. Two cases of fatal myelopathy were observed after spinal cord doses within the highest tertile (41.4 cobalt Gy equivalent and 36 Gy). CONCLUSIONS Peri-transplant RT was used for high-risk disease. Oncologic outcomes after RT were encouraging. However, 2 cases of grade 5 myelopathy were observed. If used cautiously, RT may contribute to durable remission in patients at high risk of relapse.
-
3.
Anti-CD25 Radioimmunotherapy with BEAM Autologous Hematopoietic Cell Transplantation Conditioning in Hodgkin Lymphoma
Herrera, A. F., Palmer Ph, D. Jm, Adhikarla, V., Yamauchi, D. M., Poku, E. K., Bading, J., Yazaki, P., Dandapani, S., Mei, M. G., Chen, R. W., et al
Blood advances. 2021
Abstract
High-risk relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) is associated with poor outcomes after conventional salvage therapy and autologous hematopoietic cell transplantation (AHCT). Post-AHCT consolidation with brentuximab vedotin (BV) improves progression-free survival (PFS), but with increasing use of BV early in the treatment course, the utility of consolidation is unclear. CD25 is often expressed on Reed-Sternberg cells and in the tumor microenvironment in HL and we hypothesized that the addition of 90Y-antiCD25 (aTac) to BEAM AHCT would be safe and result in a transplantation platform that is agnostic to prior HL-directed therapy. Twenty-five patients with high-risk R/R HL were enrolled onto this phase 1 dose-escalation trial of aTac-BEAM. Following an imaging dose of 111In-antiCD25, 2 patients had altered biodistribution and a third developed an unrelated catheter-associated bacteremia; therefore 22 patients ultimately received therapeutic 90Y-aTac-BEAM AHCT. No dose-limiting toxicities were observed and 0.6mCi/kg was deemed the recommended phase 2 dose, the dose at which the heart wall would not receive > 2500cGy. Toxicities and time to engraftment were similar to those observed with standard AHCT, though 95% of patients developed stomatitis (all grade 1-2 per Bearman toxicity scale). Seven relapses (32%) were observed, most commonly in patients with 3 or more risk factors. The estimated 5-year PFS and overall survival probabilities among 22 evaluable patients were 68% and 95%, respectively, and non-relapse mortality was 0%. aTac-BEAM AHCT was tolerable in patients with high-risk R/R HL and we are further evaluating the efficacy of this approach in a phase 2 trial. The clinical trial was registered at clinicaltrials.gov (NCT01476839).
-
4.
A Phase II Trial Evaluating The Efficacy of High-Dose Radioiodinated Tositumomab (Anti-CD20) Antibody, Etoposide and Cyclophosphamide followed by Autologous Transplantation, for High-Risk Relapsed or Refractory Non-Hodgkin's Lymphoma
Chow, V. A., Rajendran, J. G., Fisher, D. R., Appelbaum, F. R., Cassaday, R. D., Martin, P. S., Holmberg, L. A., Gooley, T. A., Stevenson, P. A., Pagel, J. M., et al
American journal of hematology. 2020
Abstract
Radiation is the most effective treatment for localized lymphoma, but treatment of multifocal disease is limited by toxicity. Radioimmunotherapy (RIT) delivers tumoricidal radiation to multifocal sites, further augmenting response by dose-escalation. This phase II trial evaluated high-dose RIT and chemotherapy prior to autologous stem-cell transplant (ASCT) for high-risk, relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity, and tolerability. Patients age < 60 years with R/R NHL expressing CD20 were eligible. Mantle cell lymphoma (MCL) patients could proceed to transplant in first remission. Patients received I-131-tositumomab delivered at ≤ 25Gy to critical normal organs, followed by etoposide, cyclophosphamide and ASCT. 107 patients were treated including aggressive lymphoma (N=29), indolent lymphoma (N=45), and MCL (N=33). After a median follow-up of 10.1 years, the 10-year PFS for the aggressive, indolent, and MCL groups were 62%, 64%, 43% respectively. The 10-year OS for the aggressive, indolent, and MCL groups were 61%, 71%, 48% respectively. Toxicities were similar to standard conditioning regimens and non-relapse mortality at 100 days was 2.8%. Late myeloid malignancies were seen in 6% patients. High-dose I-131-tositumomab, etoposide and cyclophosphamide followed by ASCT appeared feasible, safe, and effective in treating NHL, with estimated PFS at 10-years of 43-64%. In light of novel cellular therapies for R/R NHL, high-dose RIT-containing regimens yield comparable efficacy and safety and could be prospectively compared. This article is protected by copyright. All rights reserved.
-
5.
Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children's Oncology Group ANBL0532 Study
Liu, K. X., Naranjo, A., Zhang, F. F., DuBois, S. G., Braunstein, S. E., Voss, S. D., Khanna, G., London, W. B., Doski, J. J., Geiger, J. D., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco1903316
-
-
Free full text
-
Abstract
PURPOSE A primary objective of the Children's Oncology Group (COG) ANBL0532 phase III study was to assess the effect of increasing local dose of radiation to a residual primary tumor on the cumulative incidence of local progression (CILP) in patients with high-risk neuroblastoma. PATIENTS AND METHODS Newly diagnosed patients with high-risk neuroblastoma were randomly assigned or assigned to receive single or tandem autologous stem-cell transplantation (SCT) after induction chemotherapy. Local control consisted of surgical resection during induction chemotherapy and radiotherapy after last SCT. Patients received 21.6 Gy to the preoperative primary tumor volume. For patients with incomplete surgical resection, an additional boost of 14.4 Gy was delivered to the gross residual tumor, for a total dose of 36 Gy. CILP (primary end point) and event-free (EFS) and overall survival (OS; secondary end points) were compared with the COG A3973 historical cohort, in which all patients received single SCT and 21.6 Gy without a boost. RESULTS For all patients in ANBL0532 receiving radiotherapy (n = 323), 5-year CILP, EFS, and OS rates were 11.2% +/- 1.8%, 56.2% +/- 3.4%, and 68.4% +/- 3.2% compared with 7.1% +/- 1.4% (P = .0590), 47.0% +/- 3.5% (P = .0090), and 57.4% +/- 3.5% (P = .0088) for all patients in A3973 receiving radiotherapy (n = 328), respectively. Five-year CILP, EFS, and OS rates for patients in A3973 with incomplete resection and radiotherapy (n = 47) were 10.6% +/- 4.6%, 48.9% +/- 10.1%, and 56.9% +/- 10.0%, respectively. In comparison, 5-year CILP, EFS, and OS rates for patients in ANBL0532 who were randomly assigned or assigned to single SCT and received boost radiotherapy (n = 74) were 16.3% +/- 4.3% (P = .4126), 50.9% +/- 7.0% (P = .5084), and 68.1% +/- 6.7% (P = .2835), respectively. CONCLUSION Boost radiotherapy to gross residual tumor present at the end of induction did not significantly improve 5-year CILP. These results highlight the need for new strategies to decrease the risk of locoregional failure.
-
6.
Treatment patterns and disease outcomes for pediatric patients with refractory or recurrent Hodgkin lymphoma treated with curative-intent salvage radiotherapy
Tinkle, C. L., Williams, N. L., Wu, H., Wu, J., Kaste, S. C., Shulkin, B. L., Talleur, A. C., Flerlage, J. E., Hudson, M. M., Metzger, M. L., et al
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2019;134:89-95
Abstract
BACKGROUND AND PURPOSE The use of radiotherapy (RT) for pediatric patients with Hodgkin lymphoma (HL) experiencing disease progression or recurrence (15%) is controversial. We report treatment patterns and outcomes for pediatric patients with refractory/recurrent HL (rrHL) treated with curative-intent RT. MATERIALS AND METHODS Forty-six patients with rrHL treated with salvage RT at our institution were identified. All received risk-adapted, response-based frontline therapy and were retrieved with cytoreductive regimens followed by RT to failure sites, with or without autologous hematopoietic cell transplantation (AHCT). Cumulative incidence (CIN) of local failure (LF) and survival were estimated after salvage RT and regression models determined predictors of LF after salvage RT. RESULTS RT was administered as part of frontline therapy in 70% of patients, omitted for early response assessment in 13%, or deferred for primary progression in 17%. AHCT was omitted in 20% of patients. Median initial and salvage dose/site were 25.5Gy and 30.6Gy, respectively. Eight patients experienced progression. Two died without progression (median follow-up from salvage RT=3.8years). The 5-year CIN of LF after salvage RT was 17.7% (95% confidence interval [CI], 8.2-30.2%). The 5-year freedom from subsequent treatment failure and overall survival (OS) was 80.1% (95% CI, 69.2-92.6%) and 88.5% (95% CI, 79.5-98.6%), respectively. Inadequate response to salvage systemic therapy (p=0.048) and male sex (p=0.049) were significantly associated with LF after salvage RT. CONCLUSION rrHL is responsive to salvage RT, with low LF rates after moderate doses. OS is excellent, despite refractory disease. Initial salvage therapy response predicts subsequent LF.
-
7.
Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas - a single centre experience
Boltezar, L., Pintaric, K., Pretnar, J., Pohar Perme, M., Novakovic, B. J.
Radiology & Oncology. 2017;51(1):81-87
Abstract
BACKGROUND Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. PATIENTS AND METHODS Seventeen patients with FL and 29 patients with MCL were included, 15 of them were transplanted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. RESULTS The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%-96.8%) and for MCL 79.3% (95% CI 56.1%-91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%-90.3%) and for MCL 69.8% (95% CI 45.5%-84.8%), respectively. There were no secondary hematological malignancies observed in either group. CONCLUSIONS Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies.
-
8.
Comparison of Total Body Irradiation (TBI) Conditioning with Non-TBI for Autologous Stem Cell Transplantation in Newly Diagnosed or Relapsed Mature T- and NK-Cell Non-Hodgkin Lymphoma
Maeng, C. H., Ko, Y. H., Lim, D. H., Kang, E. S., Choi, J. Y., Kim, W. S., Kim, S. J.
Cancer Research & Treatment. 2017;49(1):92-103
Abstract
PURPOSE This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas. MATERIALS AND METHODS Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT. RESULTS Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non-TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non-hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than thosewho showed partial response. CONCLUSION TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas.
-
9.
Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience
Rimner, A., Lovie, S., Hsu, M., Chelius, M., Zhang, Z., Chau, K., Moskowitz, A. J., Matasar, M., Moskowitz, C. H., Yahalom, J.
International Journal of Radiation Oncology, Biology, Physics. 2017;97(5):1066-1076
Abstract
PURPOSE We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). METHODS AND MATERIALS From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board-approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. RESULTS With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. CONCLUSIONS Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.
-
10.
A multi-institutional analysis of peritransplantation radiotherapy in patients with relapsed/refractory Hodgkin lymphoma undergoing autologous stem cell transplantation
Milgrom, S. A., Jauhari, S., Plastaras, J. P., Nieto, Y., Dabaja, B. S., Pinnix, C. C., Smith, G. L., Allen, P. K., Lukens, J. N., Maity, A., et al
Cancer. , 2016 Dec 16. 2016
Abstract
BACKGROUND No consensus exists regarding the use of radiotherapy (RT) in conjunction with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with relapsed/refractory classical Hodgkin lymphoma (HL). The objectives of the current study were to characterize practice patterns and assess the efficacy and toxicity of RT at 2 major transplantation centers. METHODS Eligible patients underwent HDC/ASCT from 2006 through 2015 using the combination of either carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) or cyclophosphamide, BCNU, and etoposide (CBV). RESULTS For the cohort of 189 patients, the 4-year overall survival rate was 80%, the progression-free survival rate was 67%, and the local control (LC) rate was 68%. RT was used within 4 months of ASCT for 22 patients (12%) and was given more often for disease that was early stage, primary refractory, or [18 F]fluorodeoxyglucose (FDG)-avid at the time of HDC/ASCT. Disease recurrence occurring after HDC/ASCT was associated with primary refractory disease and FDG-avidity at the time of HDC/ASCT. RT was not found to be associated with LC, progression-free survival, or overall survival on univariate analysis. In a model incorporating primary refractory HL and FDG-avid disease at the time of HDC/ASCT, RT was found to be associated with a decreased risk of local disease recurrence (hazard ratio, 0.3; P=.02). In patients with primary refractory HL and/or FDG-avid disease at the time of HDC/ASCT, the 4-year LC rate was 81% with RT versus 49% without RT (P=.03). There was one case of Common Terminology Criteria for Adverse Events grade>3 RT-related toxicity (acute grade 3 pancytopenia). CONCLUSIONS In patients undergoing ASCT for relapsed/refractory HL, peritransplantation RT was used more often for disease that was early stage, primary refractory, or FDG-avid after salvage conventional-dose chemotherapy. RT was associated with improved LC of high-risk localized disease and was well tolerated with modern techniques. Cancer 2016. © 2016 American Cancer Society. Copyright © 2016 American Cancer Society.