scholarly journals Minimal residual disease in Acute Lymphoblastic Leukemia in the context of hematopoetic stem cell transplantation

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 30-40
Author(s):  
Maura Rosane Valério Ikoma-Colturato
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Hematopoetic Stem Cell ◽  
Specific Time Point ◽  
Hematopoetic Stem Cell Transplantation ◽  
Risk Of Relapse

Minimal or measurable residual disease (MRD) is considered the most important independent prognostic factor in acute lymphoblastic leukemia (ALL). MRD status after clinical remission has been used to establish the risk of relapse and therapeutic stratification, identifying patients who can benefit from therapeutic intensification, including allogeneic stem cell transplantation (alloSCT). The pre alloSCT MRD also identifies patients eligible for transplant and those with low or high risk of relapse after transplantation, according to the level of MRD detected. However, MRD status post-alloSCT has been shown to be a more powerful predictor of relapse than pre-transplant MRD. In addition, it is important to take into account that there are some factors to be considered to better interpret MRD information, these include: the method used for MRD assessment and its sensitivity and specificity, which may vary according to each specific time point of evaluation; the treatment regimen used; and the identification of genetic lesions that combined with MRD information can further improve the management of patients with ALL.

Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies

Blood ◽  
2012 ◽  
Vol 120 (9) ◽  
pp. 1868-1876 ◽  
Author(s):  
Nicola Gökbuget ◽  
Michael Kneba ◽  
Thorsten Raff ◽  
Heiko Trautmann ◽  
Claus-Rainer Bartram ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
High Risk Group ◽  
Molecular Response ◽  
Experimental Drugs

Abstract Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized methods and terminology in patients with Philadelphia chromosome-negative ALL. The cytologic complete response (CR) rate was 89% after induction phases 1 and 2. At this time point the molecular CR rate was 70% in 580 patients with cytologic CR and evaluable MRD. Patients with molecular CR after consolidation had a significantly higher probability of continuous complete remission (CCR; 74% vs 35%; P < .0001) and of overall survival (80% vs 42%; P = .0001) compared with patients with molecular failure. Patients with molecular failure without stem cell transplantation (SCT) in first CR relapsed after a median time of 7.6 months; CCR and survival at 5 years only reached 12% and 33%, respectively. Quantitative MRD assessment identified patients with molecular failure as a new high-risk group. These patients display resistance to conventional drugs and are candidates for treatment with targeted, experimental drugs and allogeneic SCT. Molecular response was shown to be highly predictive for outcome and therefore constitutes a relevant study end point. The studies are registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.

scholarly journals ROLE OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014065 ◽  
Author(s):  
Federico Lussana ◽  
Alessandro Rambaldi
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Consolidation Therapy ◽  
Hematopoietic Stem ◽  
Risk Class

Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease, due to the expression of different biological and clinical risk factors, for which allogeneic stem cell transplantation (alloHSCT) is an effective consolidation therapy. The non-relapse mortality of alloHSCT remains significantly higher compared with that of conventional chemotherapy; therefore, one of the main challenges in the care of ALL is to establish a more precise prognostic definition to select patients who could take advantage from an alloHSCT. Currently, the use of minimal residual disease following induction and early consolidation therapy has improved the prognostic accuracy in defining ALL risk class. In Philadelphia-positive ALL, the introduction of tyrosine kinase inhibitors pre and post alloHSCT appears to improve outcomes significantly and, in the absence of specifically designed clinical trials, alloHSCT remains the most effective post- remission therapy. Nowadays, alloHSCT can be performed according to different modalities encompassing the use of different conditioning regimens, as well as different donors and stem cell source, with a significant accessibility to transplant.

scholarly journals Successful treatment of relapsed/refractory B-Acute lymphoblastic leukemia with Inotuzumab ozogamicin after blinatumomab failure

2020 ◽  
Vol 9 (2) ◽  
pp. 67-70 ◽  
Author(s):  
Sergey N. Bondarenko ◽  
Anna G. Smirnova ◽  
Ivan S. Moiseev ◽  
Bella I. Ayubova ◽  
Elena V. Babenko ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Single Cycle ◽  
Inotuzumab Ozogamicin ◽  
Hematopoietic Stem ◽  
Cell Acute Lymphoblastic Leukemia

Blinatumomab, a bispecific T-cell engaging CD3-CD19 antibody, is highly effective in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, patients who failed with Blina have a dismal outcome. Inotuzumab ozogamicin is one of the therapeutic options after blinatumomab failure. We report a young man who exhibited bone marrow (BM) relapse of B-ALL following haploidentical stem cell transplantation (haplo-HSCT). Remission was not achieved after Blinotumomab treatment, thus Inotuzumab was administered. A complete remission with no signs of minimal residual disease was achieved after a single cycle of Inotuzumab. The second haplo-HSCT from another donor was successful. Conclusion The present case demonstrate an opportunity of successful inotuzumab therapy after failure of allo-HSCT and blinotumomab treatment.

scholarly journals Evaluation and management of measurable residual disease in acute lymphoblastic leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072091002 ◽  
Author(s):  
Iman Abou Dalle ◽  
Elias Jabbour ◽  
Nicholas J. Short
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Frontline Treatment ◽  
Measurable Residual Disease

With standard chemotherapy regimens for adults with acute lymphoblastic leukemia, approximately 90% of patients achieve complete remission. However, up to half of patients have persistent minimal/measurable residual disease (MRD) not recognized by routine microscopy, which constitutes the leading determinant of relapse. Many studies in pediatric and adult populations have demonstrated that achievement of MRD negativity after induction chemotherapy or during consolidation is associated with significantly better long-term outcomes, and MRD status constitutes an independently prognostic marker, often superseding other conventional risk factors. Persistence of MRD after intensive chemotherapy is indicative of treatment refractoriness and warrants alternative therapeutic approaches including allogeneic stem cell transplantation, blinatumomab, or investigational therapies such as inotuzumab ozogamicin or chimeric antigen receptor T cells. Furthermore, the incorporation of novel monoclonal antibodies or potent BCR-ABL1 tyrosine kinase inhibitors, such as ponatinib into frontline treatment may have the advantage of achieving higher rates of MRD negativity while minimizing chemotherapy-related toxicities. Many studies are therefore ongoing to determine whether this strategy can improve cure rates without the need for allogeneic stem cell transplantation.

Sign in / Sign up

Export Citation Format

Share Document