Flow Cytometry Based MRD and Its Impact on Survival Outcome in Children and Young Adults with ALL: A Prospective Study from a Tertiary Cancer Centre in Southern India (original) (raw)
Related papers
CORRELATION OF MRD STATUS AND RELAPSE IN ACUTE MYELOID LEUKEMIA
2016
The presence of minimal residual disease (MRD) after achievement of complete remission (CR) on completion of induction therapy predict relapse in acute myeloid leukemia (AML). These results suggest a correlation between relapse and MRD at the time of morphologic remission. Here we wanted to establish the earlier supported theory whether MRD and relapse provide independent prognostic information. Patients and Methods: Analyzed data from 87 adults with AML who achieved CR after induction therapy were used. Bone marrow samples were collected after achieving complete remission and MRD was determined by 5-color multiparameter flow cytometry. Results: A total of 87 patients achieved morphological CR and 28 of which relapsed or refractory AML. 40 patients (48.2%) had flow Cytometric evidence of MRD out which 16(18.3%) relapsed, while 24(27.5%) didn't relapsed incident rate are more for MRD+ case with higher hazardous ratio. Conclusion: MRD level are linked with the prognostic factor for relapse in AML patients.
Scientific Reports, 2016
Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols. The recent increase in survival rates observed in acute lymphocytic leukemia (ALL) is due to advances in diagnosis, identification of critical prognostic factors and definition of treatment according to risk groups 1-3. At diagnosis, the most important parameters for risk stratification, with minor differences across different therapy protocols, are age, white blood cell count, immunophenotype, presence of lymphoblasts in the central nervous system and molecular analysis of chromosomal abnormalities 4,5. In addition, early response to induction chemotherapy is also a critical prognostic factor. Historically, therapeutic response was assessed mostly by morphological count of blasts in peripheral blood (PB) and bone marrow (BM). However, due to the fact that patients in morphologic remission may present morphologically undetectable amounts of residual leukemic cells, referred as "Minimal Residual Disease" (MRD), different strategies using flow cytometric or molecular techniques have been used to detect these cells in the last decades 5-7. MRD measurement is actually superior to other traditional markers of disease and based in its result, is possible to optimize chemotherapy, minimizing toxicity and decreasing risk of relapse 3-5,8,9. Current ALL protocols associate morphological analysis with MRD measurement to evaluate treatment response on both early and late time-points, providing more timely and accurate prognostic information of treatment outcome 2,4,10. However, on day 8 (D8), the earliest time point of assessment of therapeutic response, most protocols use morphological analysis of PB for risk stratification, with good and poor responses defined as
2021
Age, presenting total leukocyte counts, steroid response and cytogenetics are known prognostic markers for acute lymphoblastic leukemia (ALL). Measurable Residual Disease (MRD) (or minimal residual disease) after induction chemotherapy is well accepted prognostic markers in childhood leukemia. In resource constrained countries evaluation of MRD either not widely available or increases the cost of treatment. We retrospectively analyzed data of patients, treated with non-MRD based protocol, to see correlation of known risk factors and risk groups with end of induction MRD. Children with acute lymphoblastic leukemia treated with IC-BFM 2002 (Non-MRD based protocol) and end of the induction MRD was done. Day15 bone marrow morphology and risk groups were significantly associated with MRD level. All standard risk patients except one had MRD negative. Significant number of intermediate risk group and high risk group had positive MRD. In resource constrained settings, MRD can be avoided in ...
Indian Journal of Medical and Paediatric Oncology, 2021
Introduction The improved prognosis of pediatric B-cell acute lymphoblastic leukemia (pBALL) is considered as a good progress of medical science in the field of oncology and hematology. Minimal residual disease (MRD) refers to presence of disease in molecular level is a newer practice with respect to the detection of complete remission by conventional pathologic analysis. Prognostic value of MRD in pediatric ALL (p-ALL) is well known. Objectives This study was aimed to describe clinical outcomes and prognosis, that is, overall survival and relapse in the patients with pBALL with respect to minimal residual disease detection on day 15, day 29, and postconsolidations in a tertiary care center in eastern India. Materials and Methods Eight color flow cytometry was used to detect MRD in this study. This contained markers such as CD 19, CD 34, CD 10, CD58, CD 45, CD13, anti-TDT, CD33. Eight panels included were (1) CMPO-FITC/cCD79a-PE/cCd3ECD, (2) CD20-FITC/cCD10-PE/cCd-19ECD, (3) CD34-FITC/cCD117-PE/cCd45 ECD/CD2 PC 5, (4) CD15 FITC/ CD33PE/CD45ECD, (5) CD14 FITC/CD13 PE/CD45ECD, (6) HLADR FITC/ CD7 PE/CD45 ECD, (7) TdT FITC/CD45 ECD (IF CD34 NEG), and (8) CD58 FITC/CD 45 ECD (IF BOTH CD34 AND TdT NEG; were used to prepare the marker. Results The study included 52 patients. In the 52 patients, 59.6% patients are alive with a p-value of 0.031. MRD was checked on every 15th and the 29th day and postconsolidation of the treatment where in day 15 (p = 0.023), it was 53.4% positive and 46.5% negative. On day 29 (p = 0.031), MRD was 22.5% positive and 77.5% negative, in post consolidation, it was positive in 20% and negative is 80%. MRD value below 0.01 is taken as negative and above is taken as positive. The overall survival (OS) is of 32.88 + 8.59 with a 6 to 36 months of duration. In relapsed cases, no hemorrhagic relapse was found and two CNS relapses were found. Conclusion It was a study of 52 patients of pBALL with a detection of MRD by FCM. MRD-negative patients had a good prognosis and comparatively lower rate of relapse than the one with positive MRD. Effort should be made to adhere to recommendation of MRD testing in clinical guidelines.
World J Pediatr, 2007
Ob bj je ec ct ti iv ve e: : Improvements in the treatment of childhood acute lymphoblastic leukemia (ALL) provide a complete remission in many patients. Several study groups indicated that determining submicroscopic levels of leukemia cells in the bone marrow (minimal residual disease-MRD) on day 15 is affects the prognosis. Flow cytometry (FCM) is a fast and cheap approach when compared to other molecular methods. In this study, day 15 bone marrow MRD levels and demographic profile in BALL patients assessed in our laboratory between December 2010 and August 2011 were discussed. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Bone marrow samples obtained on treatment day 0 and 15 from patients diagnosed with ALL (n=45) and the expressions of CD10, CD11a, CD19, CD20, CD34, CD38, CD45 and CD58 have been determined using FACSCalibur according to the Associazione Italiana Ematologia Oncologia Pediatrica-Berlin Frankfurt Münster (AIEOP-BFM) protocol and evaluated by CELLQuest-Pro software. After determination of the number of nucleated cells with Syto16, the percentages of leukemic cells (blast-MRD percentage) detected in the nucleated CD19+ B cell population were classified as flow low (FLR), flow medium (FMR) and flow high (FHR) risk. R Re es su ul lt ts s: : Six of the 45 cases (10 females, 35 males, 6.17±3.90 years) in our survey were MRD negative and 39 were positive. Eleven cases were determined as FLR (24.4%), 26 as FMR (57.8%) and 8 as FHR (17.8%) according to MRD risk. C Co on nc cl lu us si io on n: : All of the evaluations were approved by an AIEOP-BFM partner (100%). Since 30 August 2011, our institute has become the first center in Turkey to evaluate its own cases with the qualifications of our AIEOP-BFM partner (Vienna). In the future, we plan to investigate correlation of MRD-FCM results with prognosis and relapse, and to compare these findings with the polymerase chain reaction results. K Ke ey y W Wo or rd ds s: : AIEOP protocol 8202; flow cytometry; leukemia, B-cell Ö ÖZ ZE ET T A Am ma aç ç: : Çocukluk çağı akut lenfoblastik lösemi (ALL) tedavisindeki ilerlemeler hastaların çoğunda tam remisyon sağlamaktadır. Farklı çalışma grupları tedavinin 15. gününde kemik iliğinde lösemi hücrelerinin submikroskobik düzeylerinin saptanmasının (minimal kalıt hastalık, MRD) prognoz ile ilişkili olduğunu göstermiştir. Flow sitometri (FCM), moleküler yöntemlerle karşılaştırıldığında daha hızlı ve ucuzdur. Günümüzde 100'den fazla merkezde uygulanmakta olan MRD-FCM yöntemi, lösemi tedavi eden farklı merkezlerden gönderilen örneklerde çalışmak üzere Türkiye'de ilk kez enstitümüzde başlatılmıştır. Bu makalede Aralık 2010-Ağutos 2011 tarihleri arasında laboratuarımızda değerlendirilen BALL olgularının 15. gün kemik iliği örneklerinde MRD düzeyleri ve demografik özellikleri tartışılmıştır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : AALL tanısı almış hastalardan (n=45) tedavinin 0. ve 15. gününde alınan kemik iliği örneklerinde CD10, CD11a, CD19, CD20, CD34, CD38, CD45 ve CD58 ekspresyonu FACSCalibur cihazı ile Associazione Italiana Ematologia Oncologia Pediatrica-Berlin Frankfurt Münster (AIEOP-BFM) protokolüne göre saptanmış, elde edilen veriler CELLQuest-Pro yazılımı ile değerlendirilmiştir. Çekirdekli hücre sayısı Syto16 ile belirlendikten sonra, çekirdekli CD19+ B hücre popülasyonu içinde saptanan lösemik hücrelerin tüm çekirdekli hücrelere oranı (% blast-MRD) hesaplanmış, flow düşük (FLR), orta (FMR) ve yüksek (FHR) risk olarak sınıflandırılmıştır. B Bu ul lg gu ul la ar r: : Çalışmamızdaki 45 olgudan (10 kız, 35 erkek, 6,17±3,90 yıl) altısı MRD negatif, 39 olgu ise pozitiftir. MRD risk skorlamasına göre 11 olgu FLR (%24,4), 26 olgu FMR (%57,8) ve 8 olgu FHR (%17,8) olarak saptanmıştır. S So on nu uç ç: : Değerlendirmelerin hepsi AIEOP-BFM partner (Viyana) tarafından onaylanmış (%100) ve merkezimiz AIEOP-BFM partnerin denetiminde 30 Ağustos 2011 tarihinde yeterlilik kazanarak kendi olgularını değerlendirebilen Türkiye'deki ilk merkez olmuştur. Yeni çalışmalardan elde edilecek veriler doğrultusunda MRD-FCM sonuçlarının prognoz ve relaps ile ilişkisinin, polimeraz zincir reaksiyonu sonuçları ile uyumunun araştırılması hedeflenmektedir.
British Journal of Haematology, 2008
The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17-60 years), 116 patients were suitable for analysis. MRD level ‡0AE1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0AE0001), as well as in the standard risk (SR, P = 0AE0003) and high-risk (P = 0AE008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0AE1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0AE001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.