scholarly journals CAR‐T therapy bridging to allogeneic HSCT provides durable molecular remission of Ph + mixed phenotype acute leukaemia with minimal residual disease

2020 ◽  
Vol 191 (2) ◽  
Author(s):  
Danqing Kong ◽  
Changju Qu ◽  
Haiping Dai ◽  
Zheng Li ◽  
Jia Yin ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Acute Leukaemia ◽  
Residual Disease ◽  
Molecular Remission ◽  
Allogeneic Hsct ◽  
Car T ◽  
Mixed Phenotype ◽  
Minimal Residual

scholarly journals Dasatinib for a child with Philadelphia chromosome–positive acute lymphoblastic leukemia and persistently elevated minimal residual disease during imatinib therapy

2015 ◽  
Vol 22 (4) ◽  
pp. 303 ◽  
Author(s):  
K.H. Wu ◽  
H.P. Wu ◽  
T. Weng ◽  
C.T. Peng ◽  
Y.H Chao
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Intensive Chemotherapy ◽  
Molecular Remission ◽  
Allogeneic Hsct ◽  
Minimal Residual ◽  
Philadelphia Chromosome Positive

Imatinib has improved outcomes in patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (all). Minimal residual disease (mrd) is a useful tool for predicting leukemia relapse. However, there is no consensus on how to treat children with elevation of BCR-ABL transcripts but no evidence of hematologic relapse during chemotherapy combined with imatinib. Here, we report the case of a child with Ph+ all who had persistent elevation of mrd, but no evidence of hematologic relapse while receiving imatinib plus intensive chemotherapy. Dasatinib was substituted for imatinib because no suitable donor for allogeneic hematopoietic stem-cell transplantation (hsct) was available. Less-intensive chemotherapy with methotrexate and 6-mercaptopurine was administered concomitantly. No serious adverse events were encountered. With continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months. This report is the first about the long-term use of dasatinib in patients with Ph+ all and mrd elevation but hematologic remission during imatinib chemotherapy. In a similar situation, chemotherapy combined with dasatinib instead of allogeneic hsct could be considered to avoid hsct-related mortality and morbidity. Clinical trials are needed.

Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation

2019 ◽  
Vol 57 (5) ◽  
pp. 641-647 ◽  
Author(s):  
Miguel Waterhouse ◽  
Dietmar Pfeifer ◽  
Jesus Duque-Afonso ◽  
Marie Follo ◽  
Justus Duyster ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Digital Pcr ◽  
Mixed Chimerism ◽  
Clinical Samples ◽  
Molecular Remission ◽  
Remission Status ◽  
Hematopoietic Chimerism ◽  
Minimal Residual

Abstract Background Minimal residual disease (MRD) and hematopoietic chimerism testing influences clinical decision and therapeutic intervention in patients after allogeneic stem cell transplantation (HSCT). However, treatment approaches to induce complete donor chimerism and MRD negativity can lead to complications such as graft-versus-host disease (GvHD) and marrow aplasia. Therefore, there is a need for comprehensive characterization of the molecular remission status after transplantation. Methods We analyzed 764 samples from 70 patients after HSCT for the simultaneous measurement of chimerism and molecular targets used for MRD testing with a digital PCR (dPCR) platform. Results Mixed chimerism (MC) was detected in 219 samples from 37 patients. The mean percentage of host derived DNA in these clinical samples was 4.3%. Molecular relapse with a positive MRD marker and/or increased WT1 expression was observed in 15 patients. In addition to WT1 overexpression, other MRD positive markers were: NPM1 (Type A, B, K), DNMT3A (R882H), MLL-PTD, IDH1 (R132H) and KRAS (G12S). Increasing MC was observed in 15 patients. This group of patients showed either a positive MRD marker, increased WT1 expression or both. Next, we analyzed whether MC or the molecular target for MRD was first detected. MC and MRD marker positivity in this group was first detected in six and two patients, respectively. In the remaining seven patients MC and MRD positivity was detected simultaneously. Conclusions The combination of MRD and chimerism markers in a dPCR platform represents a practical, sensitive and accurate diagnostic tool for the comprehensive assessment of the molecular remission status of patients undergoing HSCT.

Minimal Residual Disease in Acute Leukaemia

2007 ◽  
pp. 561-574
Author(s):  
Letizia Foroni ◽  
Paula M Gameiro ◽  
A Victor Hoffbrand
Keyword(s):  
Minimal Residual Disease ◽  
Acute Leukaemia ◽  
Residual Disease ◽  
Minimal Residual

scholarly journals Molecular Monitoring of Minimal Residual Disease in Follicular and Mantle Cell Non-Hodgkin's Lymphomas Treated With High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Autografting

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 724-491 ◽  
Author(s):  
Paolo Corradini ◽  
Monica Astolfi ◽  
Cristina Cherasco ◽  
Marco Ladetto ◽  
Claudia Voena ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Residual Disease ◽  
Peripheral Blood Progenitor Cell ◽  
High Dose ◽  
Molecular Remission ◽  
Mantle Cell ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) was evaluated in 30 patients with follicular or mantle cell non-Hodgkin's lymphoma (NHL) undergoing an intensive treatment with high-dose sequential (HDS) chemotherapy and peripheral blood progenitor cell (PBPC) autografting. To minimize the potential tumor cell contamination, PBPC harvests were scheduled at the end of HDS pretransplant phase. All patients had advanced-stage disease and most of them presented with bone marrow (BM) involvement. A tumor marker could be generated in 90% of patients using bcl-2 or Ig heavy-chain genes. MRD was analyzed on PBPC, BM harvests, and after autografting by polymerase chain reaction (PCR). All evaluable follicular and 6 of 9 mantle cell patients achieved clinical complete remission. PCR negativity of PBPC and/or BM harvests was documented in 68% of follicular and 12% of mantle cell lymphomas. Molecular remission of PBPC and/or BM harvests was achieved in 9 of 15 patients with overt marrow involvement and in all patients with only molecular marrow infiltration at onset. Molecular follow-up was conducted on 14 patients: all 7 evaluable patients who received at least one PCR-negative graft maintained the negative status at a median follow-up of 24 months and none of them relapsed so far. Thus, the results show that (1) a molecular marker to monitor MRD can be obtained in most follicular and mantle cell NHL patients, (2) the HDS regimen may provide PCR-negative PBPC and/or BM harvests even from patients with BM disease, and (3) autograft with at least one PCR-negative harvest is associated with a durable clinical and molecular remission.

Detection of minimal residual disease in multiple myeloma and acute leukaemia

1996 ◽  
Vol 13 (2) ◽  
pp. 121-131 ◽  
Author(s):  
Marleen H. C. Bakkus ◽  
Nadine Juge-Morineau ◽  
Jutte E. Van Der Werff Ten Bosch
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Acute Leukaemia ◽  
Residual Disease ◽  
Minimal Residual
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