Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy

Champlin, Richard E.; Khouri, Issa F.; Shimoni, Avichai; Gajewski, James; Kornblau, Steven M.; Molldrem, Jeffrey J.; Ueno, Naoto T.; Giralt, Sergío; Anderlini, Paolo

doi:10.1046/j.1365-2141.2000.02196.x

Cited by 179 publications

(106 citation statements)

References 111 publications

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“…The results reported here are similar to those reported by others. [2][3][4][5][6][7][12][13][14] These data undermine the use of the terms 'myeloablative' and 'nonmyeloablative'. As Deeg 15 has recently pointed out, all transplantations in patients with malignant hematological disorders are designed to be myeloablative in order to achieve disease eradication.…”

Section: Discussionmentioning

confidence: 97%

“…A limitation to our study and those of others, however, is that we did not analyze what interventions may have been prompted by the results of these chimerism studies, which may then have affected the patient's clinical outcome. As factors other than preparative regimen including primary diagnosis, previous treatment, stem cell source, cell dose, histocompatibility and GVHD prevention [1][2][3][4][5][6][7][8] are important determinants of the speed and extent of donor chimerism, the conventional reliance on type of preparative regimen alone to determine whether to perform chimerism surveillance may be oversimplified. This study suggests the need for a fresh look at present indications for surveillance of chimerism following transplantation.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT

Mickelson

Sproat

Dean

et al. 2010

Bone Marrow Transplant

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Surveillance of hematopoietic chimerism following hematopoietic SCT (HSCT) with nonmyeloablative (NMA) preparative regimens is standard to assess the need for clinical intervention. Monitoring of donor chimerism following HSCT with myeloablative (MA) preparative regimens is, however, not considered useful because engraftment is thought to occur rapidly and consistently. This study compares the timing of donor hematopoietic cell engraftment in patients undergoing NMA conditioning with fludarabine and TBI with those receiving MA conditioning with BU-or TBI-based regimens. Achievement of X90% donor leukocyte chimerism occurred rapidly and consistently in all three groups and time to achievement of X90% donor T cells was similar among the three groups (P ¼ 0.57). Achievement of X90% donor leukocyte chimerism was not associated with risk of acute or chronic GVHD, graft rejection, relapse or all cause mortality in multivariate analyses. Donor T-cell chimerism of X90% was significantly associated with development of extensive chronic GVHD. The value of routine surveillance of chimerism following any of the preparative regimens used in this study should be reevaluated.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT

Mickelson

Sproat

Dean

et al. 2010

Bone Marrow Transplant

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“…11,15 RIC regimens were developed to reduce NRM rates and to allow allogeneic SCT in elderly and medically infirm patients. 29 RIC rapidly became a promising approach to investigate in myeloma, for which NRM was historically a major limiting factor. RIC has reduced the NRM to 10% to 20%.…”

Section: Discussionmentioning

confidence: 99%

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

Shimoni

Hardan

Ayuk

et al. 2010

Cancer

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BACKGROUND: Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced-intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long-term outcome of RIC in the recurrent/refractory setting. METHODS: A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine-melphalan based conditioning and stem cell grafts from a related (n ¼ 27) or unrelated donor (n ¼ 23). RESULTS: The median age was 53 years. Forty-seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow-up of 6.4 years (range, 5-7.9 years), the overall and progression-free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7-year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome. CONCLUSIONS: Allogeneic SCT can result in long-term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010;116;3621-30.

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“…Conditioning regimens classified into TBI (10-12 Gy divided into four fractions)-based myeloablative, high-dose chemotherapy-based myeloablative and reduced-intensity regimens. 17 Supportive care had been relatively consistent throughout the study's 10-year time span. All patients received trimethoprim-sulfamethoxazole orally or inhaled pentamidine as prophylaxis against Pneumocystis jiroveci.…”

Section: Methodsmentioning

confidence: 99%

Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children

Nishio

Yagasaki

Takahashi

et al. 2009

Bone Marrow Transplant

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Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy

Cited by 179 publications

References 111 publications

Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT

Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children

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