Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT

Bader, Peter; Beck, James F.; Frey, Axel W.; Schlegel, Paul-Gerhard; Hebarth, H; Handgretinger, Rupert; Einsele, Hermann; Niemeyer, Charlotte M.; Benda, Norbert; Faul, Christoph; Kanz, Lothar; Niethammer, D.; Klingebiel, T.

doi:10.1038/sj.bmt.1701119

Cited by 192 publications

(175 citation statements)

References 29 publications

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“…The primary objective of the study was to assess engraftment and chimaerism on d +30 post transplant. In all patients, the variable number of tandem repeats polymerase chain reaction (VNTR-PCR) was used to document engraftment or residual cells of host origin (Bader et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Einsele¹,

Schäfer²,

Hebart³

et al. 2003

Br J Haematol

107

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Summary. Allogeneic stem cell transplantation (allo‐SCT) after reduced‐intensity conditioning was evaluated in 22 patients (median age 53, range 36–66 years) with multiple myeloma with progression after an autologous SCT. Seven patients received a transplant from a human leucocyte antigen (HLA)‐identical sibling and 15 patients (68%) from an unrelated donor [including 3/22 (14%) from a HLA‐mismatched unrelated donor]. Graft‐versus‐host disease (GVHD) prophylaxis consisted of serotherapy with antithymocyte globulin (ATG) and cyclosporine (CSA) (n = 12) or CSA plus mycophenolate mofetil (n = 10). Despite of heavy pretreatment, the transplant‐related mortality (TRM) for all grafted patients was acceptable at 5/22 patients (23%). Seven of 21 patients (33%) that were evaluated developed grade II GVHD and one (5%) patient developed grade III/IV acute GVHD. Seven patients developed chronic GVHD (cGVHD), but only one was extensive. Eleven patients died of progressive disease within a median of 7 months (2–19 months) post transplant. Thirteen of all 22 patients (59%) achieved a partial or complete remission with six of these 13 patients (46%) remaining event free at a median of 24 months (range 8–36 months) post allografting. Estimated 2 year overall and event‐free survival was, respectively, 25·5% and 22·0% for the whole patient group, and 62·5% and 57·1% for patients with chemosensitive disease. Chemorefractory disease prior to allogeneic stem cell transplantation (P = 0·0182) and absence of cGVHD (P = 0·069) were associated with shorter event‐free survival. Thus long‐term disease control can be achieved, but is restricted to patients responding to prior salvage chemotherapy.

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Section: Methodsmentioning

confidence: 99%

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Einsele¹,

Schäfer²,

Hebart³

et al. 2003

Br J Haematol

107

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“…Chimerism of donor cells was analyzed in mononuclear cells using microsatellite markers as described in detail previously. 18 …”

Section: Patient Populationmentioning

confidence: 99%

Influence of age on outcome after allogeneic hematopoietic cell transplantation: a single center study in patients aged ⩾60

Federmann

Faul

Meisner

et al. 2015

Bone Marrow Transplant

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Reduced intensity conditioning regimens lead to an increasing use of allogeneic hematopoietic cell transplantation (HCT) in elderly patients. We retrospectively analyzed 151 patients aged ⩾ 60 receiving allogeneic HCT 2000-2012 at our center. Median age was 66 years. Kaplan-Meier estimated 3-year OS was 42% with a median follow-up of 38 months. Cumulative incidences of progression and non-relapse mortality after 3 years were 38 and 24%. OS was better in the group of patients 465 years with a Kaplan-Meier estimated OS of 50% vs 34%, P = 0.060. We observed a significant influence of donor age (o 50 years: 53% vs 450 years: 30%, P = 0.017) and gender match (matched: 57% vs mismatched: 32%, P = 0.007) on outcome. The use of a matched related donor was inferior compared with a matched or mismatched unrelated donor (19% vs 47%, P = 0.015). On multivariate analysis there was an increased hazard ratio for a non-gender-matched HLA-matched-related donor (hazard ratio 3.23, 95% confidence interval 1.55-6.74, P = 0.002). Age had no significant impact on OS (P = 0.414). In conclusion, the data suggest that older age alone has no negative impact on the outcome of allogeneic HCT. Transplant decision should be tailored to disease risk and patient performance status rather than age.

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“…The first rituximab infusion was given in combination with 185 MBq (5 mCi) Monitoring of patients for engraftment, chimerism, disease, toxicity and donor lymphocyte infusions (DLIs) Hematopoietic donor cell chimerism was monitored every 4 weeks in all patients using microsatellite markers as described. 11 Engraftment was assessed by peripheral blood cell counts. Engraftment was defined as the first day on which the absolute neutrophil count was consistently over 500 absolute neutrophil count/mL.…”

Section: Dosimetry Conditioning Regimen and Transplantationmentioning

confidence: 99%

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

Bethge

Harsdorf

Bornhäuser

et al. 2012

Bone Marrow Transplant

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A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n ¼ 5) or matched-unrelated donors (n ¼ 15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n ¼ 13), transformed CLL (n ¼ 4), blastic mantle cell lymphoma (n ¼ 2) and follicular lymphoma grade 3 (n ¼ 1). Median age was 51 (range, 29-69) years. All patients were high risk with relapsed/ refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006-1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II-IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan-Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.

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Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT

Cited by 192 publications

References 29 publications

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Influence of age on outcome after allogeneic hematopoietic cell transplantation: a single center study in patients aged ⩾60

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

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