Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.

Khouri, Issa F.; Keating, Michael J.; Körbling, Martin; Przepiorka, Donna; Anderlini, Paolo; O'Brien, S; Giralt, Sergío; Ippoliti, Cindy; Wolff, B. Von; Gajewski, James; Donato, Michèle; Claxton, David F.; Ueno, Naoto T.; Andersson, Börje S.; Gee, A; Champlin, Richard E.

doi:10.1200/jco.1998.16.8.2817

Cited by 857 publications

(520 citation statements)

References 32 publications

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“…To overcome this obstacle, allogeneic HSCT with a reduced-intensity (RIST) or nonmyeloablative conditioning regimen has recently been explored for patients who are ineligible to receive conventional myeloablative HSCT (CIST) due to age limits or comorbidities. Many studies suggested that RIST is a reasonable option for older patients or patients with comobidities with acceptable treatment-related complications or morbidity, while preserving adequate antitumor effects [1][2][3][4][5][6][7][8][9][10][11][12]. However, these studies mostly pursued different variables including disease types, stages [1,4-6, 8,12], donor type [1,2,5,10], graft source [1,2], conditioning regimens [4,5,7,9], and/or GvHD prophylaxis [1,4,9].…”

Section: Introductionmentioning

confidence: 99%

Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan

Saito

Kami

Mori³

et al. 2007

American J Hematol

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This prospective trial assessed the safety and efficacy of allogeneic hematopoietic stem cell transplantation from a HLA-matched donor with a reduced-intensity regimen (RIST) consisting of iv fludarabine 30 mg/m 2 for 6 days and oral busulfan 4 mg/kg/day for 2 days in patients older than 50 years with hematological malignancies. Cyclosporine alone or cyclosporine with short-term methotrexate was randomized for graftversus-host disease prophylaxis. After 30 patients had been enrolled, an interim analysis was performed, and this report focuses on a precise evaluation of the toxicity profile and chimerism kinetics. Sustained engraftment in all patients, no severe regimen-related toxicity (RRT) within 20 days, and no transplantrelated mortality through Day 100 were observed. T-cell (CD3+) full-donor (over 90%) chimerism was observed in 22 of the 30 patients, while the remaining eight had mixed-donor chimerism over 77% on Day 90. Thereafter, five subsequently converted to full-donor chimerism without donor lymphocyte infusion by day 120 (n = 4) or Day 180 (n = 1). Two showed persistent mixed chimerism without relapse through Day 180. Grade III-IV acute graft-versus-host disease and extensive chronic graft-versus-host disease occurred in 10% and 73%, respectively. With a median follow-up of 1.5 years, overall survival and disease-free survival at 1 year was 83% and 62%, respectively. Seven patients hematologically relapsed overall, and five of them had myelodysplastic syndrome with poor prognostic factors. In older patients, RIST with fludarabine and busulfan was associated with acceptable toxicities and a satisfactory antileukemia effect, regardless of the early chimerism status. Am. J. Hematol. 82:873-880, 2007. V

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Section: Introductionmentioning

confidence: 99%

Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan

Saito

Kami

Mori³

et al. 2007

American J Hematol

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“…In an attempt to extend the use of allogeneic HCT to older patients and those with comorbid conditions, several groups of investigators have explored allogeneic HCT after reduced-intensity [8][9][10] or truly nonmyeloablative conditioning regimens [11][12][13][14] in which the burden of tumour eradication was shifted toward GVT effects.…”

Section: Centermentioning

confidence: 99%

Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning

2005

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Summary Nonmyeloablative or reduced-intensity conditioning regimens have been used to condition elderly or ill patients with hematological malignancies for allogeneic hematopoietic cell transplantation (HCT). Initial mixed donor/host chimerism (i.e. the coexistence of hematopoietic cells of host and donor origin) has been observed in most patients after such transplants. Here, we describe both factors affecting engraftment kinetics in patients given a nonmyeloablative or a reduced-intensity conditioning, and associations between peripheral blood cell subset chimerism levels and HCT outcomes. c 2004 Elsevier Ltd. All rights reserved. KEYWORDSHematopoietic cell transplantation; Nonmyeloablative; Chimerism; Engraftment Reduced-intensity and nonmyeloablative conditioning regimens for allogeneic HCTTo avoid serious regimen-related toxicities, the use of conventional allogeneic hematopoietic cell transplantation (HCT) has been restricted to younger and medically fit patients. 1 This is unfortunate since the median age at diagnosis for patients with hematological malignancies such as acute and chronic leukemias, lymphomas, multiple myeloma or myelodysplastic syndromes, ranges from 65 to 70 years, 2 thereby precluding the use of allogeneic HCT for most patients with these diseases. The curative potential of allogeneic HCT has been ascribed not only to the eradication of malignant cells by high-dose chemotherapy and total body irradiation, but also to immune-mediated graft-versustumor (GVT) effects. [3][4][5] The power of the 0268-960X/$ -see front matter c

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“…Furthermore, recently, non-myeloablative drug combinations as a regimen for allogeneic hematopoietic stem cell transplantation have been used extensively to reduce regimen related toxicity, including cardiotoxicity [36][37][38]. Nishio et al reported successful nonmyeloablative stem cell transplantation in a case with severe aplastic anemia complicated by heart failure [39].…”

Section: Discussionmentioning

confidence: 99%

Predictive value of QT dispersion for acute heart failure after autologous and allogeneic hematopoietic stem cell transplantation

et al. 2004

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The aim of our study was to evaluate whether corrected QT dispersion (QTc dispersion), an electrocardiographic marker, is a good predictor of the development of acute heart failure after high-dose chemotherapy followed by autologous or allogeneic hematopoietic stem cell transplantation. We enrolled 50 consecutive patients, from age 15 to 63 years, with hematopoietic diseases scheduled to undergo autologous or allogeneic hematopoietic stem cell transplantation, and compared QTc dispersion with other markers before transplantation conditioning. In univariate logistic analysis, QTc dispersion was a significant factor for acute heart failure after hematopoietic stem cell transplantation (odds ratio, 3.7 per 10 msec; confidence interval, 1.6-8.5; P = 0.002). There were no significant differences as age, sex, systolic or diastolic echocardiographic function markers, cumulative anthracycline dose, or QTc before transplantation between patients with and without acute heart failure. After multiple adjustments for left ventricular ejection fraction, cumulative anthracycline dose, cyclophosphamide conditioning dose, QTc dispersion was a significant and independent factor for acute heart failure after hematopoietic stem cell transplantation (odds ratio, 48.0 per 10 msec; confidence interval, 1.4-1666.3; P = 0.03). This study demonstrated that QTc dispersion could be used as a powerful noninvasive predictor of the development of acute heart failure after hematopoietic stem cell transplantation. Am.

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Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.

Cited by 857 publications

References 32 publications

Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan

Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan

Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning

Predictive value of QT dispersion for acute heart failure after autologous and allogeneic hematopoietic stem cell transplantation

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