Patterns of Failure and Survival Outcomes after Total Lymphoid Irradiation and High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Relapsed or Refractory Classical Hodgkin Lymphoma

Nitika Paudel, Derek Schulze, Ryan D. Gentzler, Andrew M. Evens, Irene Helenowski, Gary L Dillehay, Olga Frankfurt, Jayesh Mehta, Eric Donald Donnelly, Leo I Gordon, Jane Norma Winter, Bharat B Mittal*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Purpose: The patterns of failure and long-term outcomes of patients with relapsed or refractory classical Hodgkin lymphoma treated with total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous stem cell transplantation (aSCT) are reported. Methods and Materials: Patients with biopsy-proven primary refractory or relapsed classical Hodgkin lymphoma who received salvage chemotherapy and accelerated hyperfractionated TLI before high-dose chemotherapy and aSCT were included. Patterns of failure were delineated after fusing pretransplant planning computed tomography to the scan reporting the first failure. Survival rates were computed using the Kaplan-Meier method. Multivariate analysis using proportional hazards regression was done to determine prognostic factors for overall survival (OS) and progression-free survival (PFS). Results: Between 1993 and 2016, 89 patients underwent salvage treatments. Twenty patients failed at a median of 6.1 months after aSCT. Posttreatment scans were available for 16 patients who failed in a combined 43 different sites, 11 of which were extranodal. Patients failed at multiple sites, mostly within radiation fields. The 5-, 10-, and 15-year OS rates were 72.8%, 68.0%, and 58.3%; PFS rates were 73.3%, 68.5%, and 58.7%; event-free survival rates were 72.3%, 67.5%, and 57.8% respectively. The 5- and 10- year actuarial local control rates were both 77.6%. Complete response (CR) to salvage chemotherapy was associated with statistically significant improvements in OS and PFS. Eight patients developed secondary malignancies; 5 were hematologic and 3 were solid tumors. Conclusions: Most failures were within the irradiated volume, which reflects the treatment-resistant disease biology. As part of a conditioning regimen, TLI yields good survival outcomes, particularly in patients achieving CR before transplant. However, need for RT in this setting should be assessed and new strategies should be developed to combat the treatment-resistant biology, especially in patients with less than CR after salvage chemotherapy.

Original languageEnglish (US)
Pages (from-to)436-446
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Volume104
Issue number2
DOIs
StatePublished - Jun 1 2019

Fingerprint

Lymphatic Irradiation
transplantation
stem cells
Stem Cell Transplantation
refractories
chemotherapy
Hodgkin Disease
Drug Therapy
dosage
irradiation
Survival
Disease-Free Survival
Survival Rate
progressions
biology
Salvage Therapy
combat
conditioning
radiation distribution
hazards

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

@article{335e6b37575843adaeff5db2517aa95d,
title = "Patterns of Failure and Survival Outcomes after Total Lymphoid Irradiation and High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Relapsed or Refractory Classical Hodgkin Lymphoma",
abstract = "Purpose: The patterns of failure and long-term outcomes of patients with relapsed or refractory classical Hodgkin lymphoma treated with total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous stem cell transplantation (aSCT) are reported. Methods and Materials: Patients with biopsy-proven primary refractory or relapsed classical Hodgkin lymphoma who received salvage chemotherapy and accelerated hyperfractionated TLI before high-dose chemotherapy and aSCT were included. Patterns of failure were delineated after fusing pretransplant planning computed tomography to the scan reporting the first failure. Survival rates were computed using the Kaplan-Meier method. Multivariate analysis using proportional hazards regression was done to determine prognostic factors for overall survival (OS) and progression-free survival (PFS). Results: Between 1993 and 2016, 89 patients underwent salvage treatments. Twenty patients failed at a median of 6.1 months after aSCT. Posttreatment scans were available for 16 patients who failed in a combined 43 different sites, 11 of which were extranodal. Patients failed at multiple sites, mostly within radiation fields. The 5-, 10-, and 15-year OS rates were 72.8{\%}, 68.0{\%}, and 58.3{\%}; PFS rates were 73.3{\%}, 68.5{\%}, and 58.7{\%}; event-free survival rates were 72.3{\%}, 67.5{\%}, and 57.8{\%} respectively. The 5- and 10- year actuarial local control rates were both 77.6{\%}. Complete response (CR) to salvage chemotherapy was associated with statistically significant improvements in OS and PFS. Eight patients developed secondary malignancies; 5 were hematologic and 3 were solid tumors. Conclusions: Most failures were within the irradiated volume, which reflects the treatment-resistant disease biology. As part of a conditioning regimen, TLI yields good survival outcomes, particularly in patients achieving CR before transplant. However, need for RT in this setting should be assessed and new strategies should be developed to combat the treatment-resistant biology, especially in patients with less than CR after salvage chemotherapy.",
author = "Nitika Paudel and Derek Schulze and Gentzler, {Ryan D.} and Evens, {Andrew M.} and Irene Helenowski and Dillehay, {Gary L} and Olga Frankfurt and Jayesh Mehta and Donnelly, {Eric Donald} and Gordon, {Leo I} and Winter, {Jane Norma} and Mittal, {Bharat B}",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.ijrobp.2019.02.007",
language = "English (US)",
volume = "104",
pages = "436--446",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Patterns of Failure and Survival Outcomes after Total Lymphoid Irradiation and High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Relapsed or Refractory Classical Hodgkin Lymphoma

AU - Paudel, Nitika

AU - Schulze, Derek

AU - Gentzler, Ryan D.

AU - Evens, Andrew M.

AU - Helenowski, Irene

AU - Dillehay, Gary L

AU - Frankfurt, Olga

AU - Mehta, Jayesh

AU - Donnelly, Eric Donald

AU - Gordon, Leo I

AU - Winter, Jane Norma

AU - Mittal, Bharat B

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Purpose: The patterns of failure and long-term outcomes of patients with relapsed or refractory classical Hodgkin lymphoma treated with total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous stem cell transplantation (aSCT) are reported. Methods and Materials: Patients with biopsy-proven primary refractory or relapsed classical Hodgkin lymphoma who received salvage chemotherapy and accelerated hyperfractionated TLI before high-dose chemotherapy and aSCT were included. Patterns of failure were delineated after fusing pretransplant planning computed tomography to the scan reporting the first failure. Survival rates were computed using the Kaplan-Meier method. Multivariate analysis using proportional hazards regression was done to determine prognostic factors for overall survival (OS) and progression-free survival (PFS). Results: Between 1993 and 2016, 89 patients underwent salvage treatments. Twenty patients failed at a median of 6.1 months after aSCT. Posttreatment scans were available for 16 patients who failed in a combined 43 different sites, 11 of which were extranodal. Patients failed at multiple sites, mostly within radiation fields. The 5-, 10-, and 15-year OS rates were 72.8%, 68.0%, and 58.3%; PFS rates were 73.3%, 68.5%, and 58.7%; event-free survival rates were 72.3%, 67.5%, and 57.8% respectively. The 5- and 10- year actuarial local control rates were both 77.6%. Complete response (CR) to salvage chemotherapy was associated with statistically significant improvements in OS and PFS. Eight patients developed secondary malignancies; 5 were hematologic and 3 were solid tumors. Conclusions: Most failures were within the irradiated volume, which reflects the treatment-resistant disease biology. As part of a conditioning regimen, TLI yields good survival outcomes, particularly in patients achieving CR before transplant. However, need for RT in this setting should be assessed and new strategies should be developed to combat the treatment-resistant biology, especially in patients with less than CR after salvage chemotherapy.

AB - Purpose: The patterns of failure and long-term outcomes of patients with relapsed or refractory classical Hodgkin lymphoma treated with total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous stem cell transplantation (aSCT) are reported. Methods and Materials: Patients with biopsy-proven primary refractory or relapsed classical Hodgkin lymphoma who received salvage chemotherapy and accelerated hyperfractionated TLI before high-dose chemotherapy and aSCT were included. Patterns of failure were delineated after fusing pretransplant planning computed tomography to the scan reporting the first failure. Survival rates were computed using the Kaplan-Meier method. Multivariate analysis using proportional hazards regression was done to determine prognostic factors for overall survival (OS) and progression-free survival (PFS). Results: Between 1993 and 2016, 89 patients underwent salvage treatments. Twenty patients failed at a median of 6.1 months after aSCT. Posttreatment scans were available for 16 patients who failed in a combined 43 different sites, 11 of which were extranodal. Patients failed at multiple sites, mostly within radiation fields. The 5-, 10-, and 15-year OS rates were 72.8%, 68.0%, and 58.3%; PFS rates were 73.3%, 68.5%, and 58.7%; event-free survival rates were 72.3%, 67.5%, and 57.8% respectively. The 5- and 10- year actuarial local control rates were both 77.6%. Complete response (CR) to salvage chemotherapy was associated with statistically significant improvements in OS and PFS. Eight patients developed secondary malignancies; 5 were hematologic and 3 were solid tumors. Conclusions: Most failures were within the irradiated volume, which reflects the treatment-resistant disease biology. As part of a conditioning regimen, TLI yields good survival outcomes, particularly in patients achieving CR before transplant. However, need for RT in this setting should be assessed and new strategies should be developed to combat the treatment-resistant biology, especially in patients with less than CR after salvage chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=85062810944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062810944&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2019.02.007

DO - 10.1016/j.ijrobp.2019.02.007

M3 - Article

VL - 104

SP - 436

EP - 446

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 2

ER -