Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy

I. F. Khouri, M. S. Lee, J. Romaguera, N. Mirza, H. Kantarjian, M. Korbling, M. Albitar, S. Giralt, B. Samuels, P. Anderlini, J. Rodriguez, B. Von Wolff, J. Gajewski, F. Cabanillas, R. Champlin

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Background: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus- lymphoma effect in such patients post allogeneic hematopoietic transplantation. Patients and methods: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. Results: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non- responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%,- 100%) compared with 44% (95% CI: 1%88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). Conclusions: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

Original languageEnglish (US)
Pages (from-to)1293-1299
Number of pages7
JournalAnnals of Oncology
Volume10
Issue number11
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Mantle-Cell Lymphoma
Homologous Transplantation
Transplants
Neoplasms
Graft vs Host Disease
Polymerase Chain Reaction
Whole-Body Irradiation
Cytarabine
Confidence Intervals
Cyclophosphamide
Lymphoma
Transplantation
bcl-1 Genes
Immunoglobulin Genes
Survival
Gene Rearrangement
Autologous Transplantation
Vincristine
Hematologic Neoplasms
HLA Antigens

Keywords

  • Allogeneic transplantation for mantle-cell lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Khouri, I. F., Lee, M. S., Romaguera, J., Mirza, N., Kantarjian, H., Korbling, M., ... Champlin, R. (1999). Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy. Annals of Oncology, 10(11), 1293-1299. https://doi.org/10.1023/A:1008380527502

Allogeneic hematopoietic transplantation for mantle-cell lymphoma : Molecular remissions and evidence of graft-versus-malignancy. / Khouri, I. F.; Lee, M. S.; Romaguera, J.; Mirza, N.; Kantarjian, H.; Korbling, M.; Albitar, M.; Giralt, S.; Samuels, B.; Anderlini, P.; Rodriguez, J.; Von Wolff, B.; Gajewski, J.; Cabanillas, F.; Champlin, R.

In: Annals of Oncology, Vol. 10, No. 11, 1999, p. 1293-1299.

Research output: Contribution to journalArticle

Khouri, IF, Lee, MS, Romaguera, J, Mirza, N, Kantarjian, H, Korbling, M, Albitar, M, Giralt, S, Samuels, B, Anderlini, P, Rodriguez, J, Von Wolff, B, Gajewski, J, Cabanillas, F & Champlin, R 1999, 'Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy', Annals of Oncology, vol. 10, no. 11, pp. 1293-1299. https://doi.org/10.1023/A:1008380527502
Khouri, I. F. ; Lee, M. S. ; Romaguera, J. ; Mirza, N. ; Kantarjian, H. ; Korbling, M. ; Albitar, M. ; Giralt, S. ; Samuels, B. ; Anderlini, P. ; Rodriguez, J. ; Von Wolff, B. ; Gajewski, J. ; Cabanillas, F. ; Champlin, R. / Allogeneic hematopoietic transplantation for mantle-cell lymphoma : Molecular remissions and evidence of graft-versus-malignancy. In: Annals of Oncology. 1999 ; Vol. 10, No. 11. pp. 1293-1299.
@article{eb6a314ee7e04c5f90d7b39a7734de1c,
title = "Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy",
abstract = "Background: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus- lymphoma effect in such patients post allogeneic hematopoietic transplantation. Patients and methods: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. Results: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7{\%}) achieved complete and two (14.3{\%}) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non- responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55{\%} (95{\%} confidence interval (95{\%} CI): 28{\%}-83{\%}). For patients with chemosensitive disease, FFP and OS at one year were both 90{\%} (95{\%} CI: 71{\%},- 100{\%}) compared with 44{\%} (95{\%} CI: 1{\%}88{\%}) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). Conclusions: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.",
keywords = "Allogeneic transplantation for mantle-cell lymphoma",
author = "Khouri, {I. F.} and Lee, {M. S.} and J. Romaguera and N. Mirza and H. Kantarjian and M. Korbling and M. Albitar and S. Giralt and B. Samuels and P. Anderlini and J. Rodriguez and {Von Wolff}, B. and J. Gajewski and F. Cabanillas and R. Champlin",
year = "1999",
doi = "10.1023/A:1008380527502",
language = "English (US)",
volume = "10",
pages = "1293--1299",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Allogeneic hematopoietic transplantation for mantle-cell lymphoma

T2 - Molecular remissions and evidence of graft-versus-malignancy

AU - Khouri, I. F.

AU - Lee, M. S.

AU - Romaguera, J.

AU - Mirza, N.

AU - Kantarjian, H.

AU - Korbling, M.

AU - Albitar, M.

AU - Giralt, S.

AU - Samuels, B.

AU - Anderlini, P.

AU - Rodriguez, J.

AU - Von Wolff, B.

AU - Gajewski, J.

AU - Cabanillas, F.

AU - Champlin, R.

PY - 1999

Y1 - 1999

N2 - Background: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus- lymphoma effect in such patients post allogeneic hematopoietic transplantation. Patients and methods: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. Results: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non- responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%,- 100%) compared with 44% (95% CI: 1%88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). Conclusions: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

AB - Background: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus- lymphoma effect in such patients post allogeneic hematopoietic transplantation. Patients and methods: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. Results: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non- responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%,- 100%) compared with 44% (95% CI: 1%88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). Conclusions: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

KW - Allogeneic transplantation for mantle-cell lymphoma

UR - http://www.scopus.com/inward/record.url?scp=0032778810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032778810&partnerID=8YFLogxK

U2 - 10.1023/A:1008380527502

DO - 10.1023/A:1008380527502

M3 - Article

C2 - 10631455

AN - SCOPUS:0032778810

VL - 10

SP - 1293

EP - 1299

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 11

ER -