Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

Anasetti, Claudio; Logan, Brent R.; Lee, Stephanie J.; Waller, Edmund K.; Weisdorf, Daniel J.; Wingard, John R.; Cutler, Corey; Westervelt, Peter; Woolfrey, Anne; Couban, Stephen; Ehninger, Gerhard; Johnston, Laura; Maziarz, Richard T.; Pulsipher, Michael A.; Porter, David; Mineishi, Shin; McCarty, John M.; Khan, Shakila P.; Anderlini, Paolo; Bensinger, William I.; Leitman, Susan F.; Rowley, Scott D.; Bredeson, Christopher; Carter, Shelly L.; Horowitz, Mary M.; Confer, Dennis L.

doi:10.1056/nejmoa1203517

Cited by 789 publications

(551 citation statements)

References 29 publications

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“…The ease with which cells can be collected from peripheral blood (PB) has led to this being the most common source of donor cells. A multicenter study randomized 551 patients (approximately half with AML of whom half were in 1st CR) to receive cells from unrelated donors' PB or bone marrow [47]. There were no differences in OS with graft failure less likely in patients receiving PB who were however more likely to have chronic graft vs. host disease (GVHD).…”

Section: Hctmentioning

confidence: 99%

Acute myeloid leukemia: 2013 update on risk‐stratification and management

2013

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Disease overviewAcute myeloid leukemia (AML) results from accumulation of abnormal blasts in the marrow. These cells interfere with normal hematopoiesis, can escape into the peripheral blood, and infiltrate CSF and lung. It is likely that many different mutations, epigenetic aberrations, or abnormalities in micro RNA expression can produce the same morphologic disease with these differences responsible for the very variable response to therapy, which is AMLs principal feature.DiagnosisThis rests on demonstration that the marrow or blood has > 20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry, with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated.Risk StratificationTwo features determine risk: the probability of treatment‐related mortality (TRM) and, more important, even in patients aged >75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics, with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogentic finding is a normal karyotype(NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics (inv 16 or t[8;21]) (60–70% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30–40% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age. Increasing evidence indicates that other mutations and abnormalities in microRNA (miRNA) expression also affect resistance as do post treatment factors, in particular the presence of minimal residual disease. These newer mutations and MRD are discussed in this update.Risk‐adapted therapyPatients with inv (16) or t(8;21) or who are NPM1+/FLT3ITD—can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg/m2 will further improve outcome in these patients. There appears no reason to use doses of cytarabine > 1 g/m2 (for example bid X 6 days), as opposed to the more commonly used 3 g/m2. Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option. This update discusses results with newer agents: quizartinib and crenolanib, gemtuzumab ozogamicin, clofarabine and cladribine, azacitidine and decitabine, volasertib, and means to prevent relapse after allogeneic transplant.The diagnosis of AML essentially is made as it was in 2012. Thus this review will emphasize new developments in risk stratification and treatment using as references many papers published in 2012. Am. J. Hematol. 88:318–327, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Hctmentioning

confidence: 99%

Acute myeloid leukemia: 2013 update on risk‐stratification and management

2013

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“…But even under these stringent matching conditions, the incidence of GVHD remains quite high (ie, 50% of patients develop grade II-IV acute GVHD, up to 35% grade III-IV acute GVHD, and 40% to 50% chronic GVHD). [8][9][10] The greater GVHD incidence in HLA allele-matched (ie, unrelated) vs haplotype-matched (ie, sibling) HCT hints at the existence of intra-major histocompatibility complex (MHC)-encoded, yet HLA-A-, HLA-B-, HLA-C-, HLA-DRB1-, and HLA-DQB1-independent (and hence hitherto unidentified), histocompatibility loci. 11,12 Other than HLA-DPB1, [13][14][15][16][17] the most promising MHC-encoded candidate is the MHC class I chain-related gene A (MICA).…”

Section: Introductionmentioning

confidence: 99%

Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Carapito

Jung

Kwemou

et al. 2016

Blood

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“…Severe acute graft-versus-host disease (GVHD) and extensive chronic GVHD (6,7) are the two main complications 32 associated to transplantation and may affect both non-relapse mortality (NRM) and quality of life. In the last years, a 33 better understanding of GVHD biology prompted the design of novel GVHD prophylaxis regimens including the use of 34 post-transplant cyclophosphamide or proteasome inhibitors, but the gold standard is still based on calcineurin inhibitors…”

mentioning

confidence: 99%

Allogeneic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas: Results of a Multicenter Phase II Prospective Trial including Rituximab in the Reduced-Intensity Conditioning Regimen

Dodero

Milone

Sarina

et al. 2017

Biology of Blood and Marrow Transplantation

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The graft versus host disease free, relapse free survival is 34% after transplantation in 2 lymphomas; 3Reduced extensive chronic GVHD with a combination of ATG and Rituximab in recipients of 4 unrelated graft 5One Rituximab Infusion prevents EBV-related lymphoproliferative disorders 6 Abstract 7The treatment of patients with refractory/relapsed B-Cell non-Hodgkin lymphoma (NHL) is evolving due to the 8 availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and 9 mortality remain a matter of concern. We conducted a multicentre prospective phase II trial to evaluate the benefit of 10 including only one dose of Rituximab (R) in the conditioning regimen before alloSCT. The primary end-point was 11 progression-free survival. The study enrolled 121 patients with relapsed/refractory B-cell lymphomas. The conditioning 12 regimen consisted of thiotepa, cyclophosphamide, fludarabine and R (500 mg/ms). Rabbit anti-thymocyte globulin 13(ATG) was administered only in case of unrelated donors. Sixty-seven (55%) and fifty-four (45%) patients received 14 grafts from related and unrelated donors, respectively. The crude cumulative incidence (CCI) of non-relapse mortality 15(NRM) was 21% at 3-years. The CCI of chronic GVHD at 3-years was 54% and 31% in recipients of matched sibling 16 and unrelated grafts, respectively. At a median follow-up of 41 months, the estimated 3-years progression-free and 17 overall survival were 50% and 61%, respectively. Long-term outcome was also evaluated with the composite end-point 18 of graft-versus-host disease-free and relapse-free survival (GRFS). This is the first work evaluating the GRFS in a 19 prospective trial of lymphomas patients: the 1 and 3-years GRFS were 40% and 34%, respectively. AlloSCT can cure a 20 fraction of patients with rather low NRM and an encouraging PFS and GRFS.

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Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

Cited by 789 publications

References 29 publications

Acute myeloid leukemia: 2013 update on risk‐stratification and management

Acute myeloid leukemia: 2013 update on risk‐stratification and management

Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Allogeneic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas: Results of a Multicenter Phase II Prospective Trial including Rituximab in the Reduced-Intensity Conditioning Regimen

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