The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation

Rohtesh S. Mehta; Antonio Di Stasi; Borje S. Andersson; Yago Nieto; Roy Jones; Marcos De Lima; Chitra Hosing; Uday Popat; Partow Kebriaei; Betul Oran; Amin Alousi; Katayoun Rezvani; Muzaffar Qazilbash; Qaiser Bashir; Catherine Bollard; Laurence Cooper; Laura Worth; Priti Tewari; Ian McNiece; Kaci Willhelm; Richard Champlin; Elizabeth J. Shpall

doi:10.1016/j.clml.2013.08.006

The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation

Rohtesh S. Mehta
, Antonio Di Stasi
, Borje S. Andersson
, Yago Nieto
, Roy Jones
, Marcos De Lima
, Chitra Hosing
, Uday Popat
, Partow Kebriaei
, Betul Oran
, Amin Alousi
, Katayoun Rezvani
, Muzaffar Qazilbash
, Qaiser Bashir
, Catherine Bollard
, Laurence Cooper
, Laura Worth
, Priti Tewari
, Ian McNiece
, Kaci Willhelm

Richard Champlin, Elizabeth J. Shpall

Research output: Contribution to journal › Comment/debate › peer-review

19 Scopus citations

Abstract

Cord blood transplantation is being used with increasing frequency for patients with high-risk hematologic malignancies. Myeloablative preparative regimens provide antitumor efficacy and facilitate engraftment but are associated with higher morbidity and nonrelapse mortality rates than nonablative regimens. We evaluated 3 sequential myeloablative regimens in the cord blood transplant setting. Regimen 1 (melphalan, fludarabine, and thiotepa) produced prompt engraftment and minimal engraftment failure but was associated with a high nonrelapse mortality rate. Regimen 2 (busulfan and fludarabine) was very well tolerated but was associated with a high rate of engraftment failure and relapse. Regimen 3 (busulfan, clofarabine, fludarabine, and low-dose total body irradiation given 9 days after the chemotherapy) was associated with a low rate of engraftment failure but was logistically difficult to administer. Finally, regimen 3 that included the total body irradiation given immediately after the chemotherapy was well tolerated, with prompt engraftment and tumor control. This latter regimen appears to be effective in preliminary studies and warrants further evaluation.

Original language	English (US)
Pages (from-to)	e1-e5
Journal	Clinical Lymphoma, Myeloma and Leukemia
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.clml.2013.08.006
State	Published - Feb 2014
Externally published	Yes

Bibliographical note

Funding Information:
The authors are grateful to the patients and their families. The authors would like to acknowledge our PharmDs, the nursing staff, research coordinators, and cell therapy laboratory staff. This work was supported in part by NCI RO1 CA061508-18 (EJS, SR), CPRIT RO1 RP100469 (EJS, SR), NCI P01 CA148600-02 (EJS, SR, CMB) and Cancer Center Core Grant CA016672 (MD Anderson investigators).

Keywords

Conditioning regimen
Hematologic malignancies
Stem cell transplant
Total body irradiation
Treatment related mortality

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10.1016/j.clml.2013.08.006

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Mehta, R. S., Di Stasi, A., Andersson, B. S., Nieto, Y., Jones, R., De Lima, M., Hosing, C., Popat, U., Kebriaei, P., Oran, B., Alousi, A., Rezvani, K., Qazilbash, M., Bashir, Q., Bollard, C., Cooper, L., Worth, L., Tewari, P., McNiece, I., ... Shpall, E. J. (2014). The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation. Clinical Lymphoma, Myeloma and Leukemia, 14(1), e1-e5. https://doi.org/10.1016/j.clml.2013.08.006

Mehta, RS, Di Stasi, A, Andersson, BS, Nieto, Y, Jones, R, De Lima, M, Hosing, C, Popat, U, Kebriaei, P, Oran, B, Alousi, A, Rezvani, K, Qazilbash, M, Bashir, Q, Bollard, C, Cooper, L, Worth, L, Tewari, P, McNiece, I, Willhelm, K, Champlin, R & Shpall, EJ 2014, 'The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation', Clinical Lymphoma, Myeloma and Leukemia, vol. 14, no. 1, pp. e1-e5. https://doi.org/10.1016/j.clml.2013.08.006

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title = "The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation",

abstract = "Cord blood transplantation is being used with increasing frequency for patients with high-risk hematologic malignancies. Myeloablative preparative regimens provide antitumor efficacy and facilitate engraftment but are associated with higher morbidity and nonrelapse mortality rates than nonablative regimens. We evaluated 3 sequential myeloablative regimens in the cord blood transplant setting. Regimen 1 (melphalan, fludarabine, and thiotepa) produced prompt engraftment and minimal engraftment failure but was associated with a high nonrelapse mortality rate. Regimen 2 (busulfan and fludarabine) was very well tolerated but was associated with a high rate of engraftment failure and relapse. Regimen 3 (busulfan, clofarabine, fludarabine, and low-dose total body irradiation given 9 days after the chemotherapy) was associated with a low rate of engraftment failure but was logistically difficult to administer. Finally, regimen 3 that included the total body irradiation given immediately after the chemotherapy was well tolerated, with prompt engraftment and tumor control. This latter regimen appears to be effective in preliminary studies and warrants further evaluation.",

keywords = "Conditioning regimen, Hematologic malignancies, Stem cell transplant, Total body irradiation, Treatment related mortality",

author = "Mehta, \{Rohtesh S.\} and \{Di Stasi\}, Antonio and Andersson, \{Borje S.\} and Yago Nieto and Roy Jones and \{De Lima\}, Marcos and Chitra Hosing and Uday Popat and Partow Kebriaei and Betul Oran and Amin Alousi and Katayoun Rezvani and Muzaffar Qazilbash and Qaiser Bashir and Catherine Bollard and Laurence Cooper and Laura Worth and Priti Tewari and Ian McNiece and Kaci Willhelm and Richard Champlin and Shpall, \{Elizabeth J.\}",

note = "Funding Information: The authors are grateful to the patients and their families. The authors would like to acknowledge our PharmDs, the nursing staff, research coordinators, and cell therapy laboratory staff. This work was supported in part by NCI RO1 CA061508-18 (EJS, SR), CPRIT RO1 RP100469 (EJS, SR), NCI P01 CA148600-02 (EJS, SR, CMB) and Cancer Center Core Grant CA016672 (MD Anderson investigators).",

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AU - Di Stasi, Antonio

AU - Andersson, Borje S.

AU - Nieto, Yago

AU - Jones, Roy

AU - De Lima, Marcos

AU - Hosing, Chitra

AU - Popat, Uday

AU - Kebriaei, Partow

AU - Oran, Betul

AU - Alousi, Amin

AU - Rezvani, Katayoun

AU - Qazilbash, Muzaffar

AU - Bashir, Qaiser

AU - Bollard, Catherine

AU - Cooper, Laurence

AU - Worth, Laura

AU - Tewari, Priti

AU - McNiece, Ian

AU - Willhelm, Kaci

AU - Champlin, Richard

AU - Shpall, Elizabeth J.

N1 - Funding Information: The authors are grateful to the patients and their families. The authors would like to acknowledge our PharmDs, the nursing staff, research coordinators, and cell therapy laboratory staff. This work was supported in part by NCI RO1 CA061508-18 (EJS, SR), CPRIT RO1 RP100469 (EJS, SR), NCI P01 CA148600-02 (EJS, SR, CMB) and Cancer Center Core Grant CA016672 (MD Anderson investigators).

PY - 2014/2

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N2 - Cord blood transplantation is being used with increasing frequency for patients with high-risk hematologic malignancies. Myeloablative preparative regimens provide antitumor efficacy and facilitate engraftment but are associated with higher morbidity and nonrelapse mortality rates than nonablative regimens. We evaluated 3 sequential myeloablative regimens in the cord blood transplant setting. Regimen 1 (melphalan, fludarabine, and thiotepa) produced prompt engraftment and minimal engraftment failure but was associated with a high nonrelapse mortality rate. Regimen 2 (busulfan and fludarabine) was very well tolerated but was associated with a high rate of engraftment failure and relapse. Regimen 3 (busulfan, clofarabine, fludarabine, and low-dose total body irradiation given 9 days after the chemotherapy) was associated with a low rate of engraftment failure but was logistically difficult to administer. Finally, regimen 3 that included the total body irradiation given immediately after the chemotherapy was well tolerated, with prompt engraftment and tumor control. This latter regimen appears to be effective in preliminary studies and warrants further evaluation.

AB - Cord blood transplantation is being used with increasing frequency for patients with high-risk hematologic malignancies. Myeloablative preparative regimens provide antitumor efficacy and facilitate engraftment but are associated with higher morbidity and nonrelapse mortality rates than nonablative regimens. We evaluated 3 sequential myeloablative regimens in the cord blood transplant setting. Regimen 1 (melphalan, fludarabine, and thiotepa) produced prompt engraftment and minimal engraftment failure but was associated with a high nonrelapse mortality rate. Regimen 2 (busulfan and fludarabine) was very well tolerated but was associated with a high rate of engraftment failure and relapse. Regimen 3 (busulfan, clofarabine, fludarabine, and low-dose total body irradiation given 9 days after the chemotherapy) was associated with a low rate of engraftment failure but was logistically difficult to administer. Finally, regimen 3 that included the total body irradiation given immediately after the chemotherapy was well tolerated, with prompt engraftment and tumor control. This latter regimen appears to be effective in preliminary studies and warrants further evaluation.

KW - Conditioning regimen

KW - Hematologic malignancies

KW - Stem cell transplant

KW - Total body irradiation

KW - Treatment related mortality

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AN - SCOPUS:84892800749

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JO - Clinical Lymphoma, Myeloma and Leukemia

JF - Clinical Lymphoma, Myeloma and Leukemia

IS - 1

ER -

The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation

Abstract

Bibliographical note

Keywords

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