Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection

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As low trough levels of mycophenolic acid (MPA) have been measured in recipients of allo-SCTs, we performed a pilot study targeting mycophenolate mofetil (MMF) doses according to the MPA area under the concentration (AUC) levels. Twenty-nine patients were transplanted from matched sibling (n ¼ 7) and unrelated donors (n ¼ 22). Tacrolimus was given orally from day À1 to achieve trough blood levels of 5-10 ng/ml. MMF was started on day 0 at 1500 mg intravenously b.i.d. AUC measurements of MPA by HPLC were scheduled on days 3, 7 and 11 after transplantation. The MMF dose was modified to achieve an MPA AUC of 35-60 lg/ml/h. With the respective adjustments 66 and 75% surpassed the lower AUC target on days 7 and 11, respectively. The cumulative incidence of grade III-IV acute GVHD was 28% (8/29). Eight out of 24 evaluable patients (33%) suffer from limited (n ¼ 3) or extensive (n ¼ 5) chronic GVHD. Overall, the results of this study suggest that targeting of MPA exposure is feasible early after transplantation. A simplified MMF targeting strategy based on MPA C max or C 2h levels seems to be warranted in future trials involving more patients at later time points in the outpatient setting.

“…The amplified fragments were examined to identify informative host or donor markers, and the respective signals were quantified, as previously described. 17 …”

Section: Engraftment and Chimerismmentioning

confidence: 99%

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Haentzschel¹,

Freiberg-Richter²,

Platzbecker³

et al. 2008

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“…Nine tetranucleotide microsatellite regions were coamplified with dye-labeled primers using the AmpFLSTR Profiler PCR amplification kit (Applied Biosystems, Weiterstadt, Germany). 17 Stable donor cell chimerism (DCC) was defined as X90% donor cell in every analyzed BM subset. In case of a DCC o90% in the CD34 þ subset and/or in unsorted BM samples (incomplete DCC), BM blast o5% and no evidence of extramedullary AML manifestation, an impending relapse was assumed.…”

Section: Post-transplant Monitoringmentioning

confidence: 99%

CD34+ lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT

Rosenow

Berkemeier

Krug

et al. 2013

After allo-SCT, analysis of CD34 þ lineage-specific donor cell chimerism (DCC) is a sensitive method for monitoring minimal residual disease in patients with AML or myelodysplastic syndrome (MDS) with CD34 expression. To substantiate evidence of whether immune interventions in patients with impending relapse, defined by incomplete lineage-specific DCC, may prevent hematological relapse, we performed a retrospective nested case control study. Unsorted and lineage-specific DCC were measured in 134 patients. Forty-three patients had an incomplete CD34 þ -DCC with no other evidence of relapse. After immediate tapering of immunosuppressive treatment (30 patients) and/or infusion of donor lymphocytes (10 patients), 21 patients remained in remission (conversion to complete lineage-specific DCC) and 22 relapsed. Relapse-free survival at 3 years of the 91 patients with stable DCC and of the 43 patients with incomplete DCC was 74% (95% confidence interval (CI), 64-83%) and 40% (95% CI, 24-58%), respectively. OS rates were 79% (95% CI, 70-88%) and 52% (95% CI, 35-69%), respectively. These results, with 49% of patients with impending relapse successfully treated with immune intervention, highly suggest that analysis of CD34 þ -DCC is an important tool for monitoring and the management of AML and MDS patients after allo-SCT.

“…Sex-matched donor-recipient chimerism was evaluated using PCR-based analyses of polymorphic minisatellite or microsatellite regions (variable number of tandem repeats (VNTRs)). 29 HLA typing was performed for patients after mismatched transplantation. 30 …”

Section: Chimerism Analysesmentioning

confidence: 99%

Idarubicin-intensified BUCY2 regimens may lower relapse rate and improve survival in patients undergoing allo-SCT for high-risk hematological malignancies: a retrospective analysis

Hong

et al. 2011

We conducted a retrospective study to evaluate the outcome of 94 consecutive patients with high-risk hematological malignancies who received allo-PBSCT, following idarubicin (IDA)-intensified BUCY2 (IDA-BUCY2) myeloablative conditioning regimens (n ¼ 53) and BUCY2 conditioning regimens (n ¼ 41). IDA 15 mg/m 2 once daily was administered by continuous infusion on days À11 to À9, followed by BU, 3.2 mg/kg in divided doses daily, on days À6 to À4, and i.v. injection of CY, 1.8 g/m 2 once daily on days À3 to À2 in the IDA-BUCY2 group. The relapse rate in patients in the IDA-BUCY2 and BUCY2-conditioning regimens group was 18.9 and 39%, respectively (P ¼ 0.030). There was no significant difference in terms of TRM. The cumulative probabilities of OS and disease-free survival at 2 years for patients conditioned with the IDA-BUCY2 and BUCY2 regimens were 65.3% vs 46.8% (P ¼ 0.038), and 63.5% vs 43.4% (P ¼ 0.025), respectively. Multivariate analysis showed that IDA-BUCY2 regimens and limited chronic GVHD were the only two factors resulting in improved survival and reduced relapse rate. This retrospective study suggests that IDA-intensified BUCY2 may be substituted for BUCY2 as conditioning regimen for patients with high-risk hematological malignancies.