However it is known that BCR-ABL1 may persist not only in leukemic cells but in myeloid and other cells. In this case MRD determined by other methods may clarify the real status of the disease. Aims: To compare results of MRD study in Ph+ B-ALL patients performed by reverse transcription PCR (RT-PCR, BCR-ABL1) and multicolor flow cytometry (MFC). Methods: The main principle of Ph+RALL-2012 is non-intensive treatment but non-interruptive with simultaneous administration of tyrosine kinase inhibitors. Study of MRD included 12 patients (m = 5, f = 7, median age = 39). MRD was determined after 36, 70, 133 and 190 days of protocol. BCR-ABL1 transcripts were evaluated by RT-PCR with sensitivity of at least 0.01%. MRD by MFC was analyzed by 6-color flow cytometry with minimal sensitivity of 0.01%. Results: On +36 day MRD analysis was performed for 8 patients. All MFC-studies were positive and MRD varied from 0.0014% to 17.5% (median = 0.22%). 7 patients had detectable BCR-ABL1 transcript (0.84% to 72.34%) and 1 patient with MFC-MRD 0.0014% was RT-PCR negative. On +70 day MRD was determined in 10 pts. Only 1 pts was MRD-negative by both methods. In 9 pts PCR-MRD was found (0.007-29.63%), but only in 5 of them MFC-MRD was positive too (0.005-5.88%). On +133 day MRD was measured in 10 patients. Two pts were PCR and MFC -negative and 8 pts had BCR-ABL1 varied from 0.008 to 0.44% but 6 of them were MFC-negative. On +190 day MRD was detected in 8 pts. MRD by PCR was found in 7 of them and MFC-MRD was positive in 2 samples. Results of two methods mismatched in 5 patients. The parallel study of MRD by MFC and RT-PCR was performed in 37 samples. The concordance of the results was in 20 cases (16 double-positive and 4 double-negative, 54%), and 16 (43%) cases were PCR + MFCand 1(2.7%) case was PCR -MFC + . The R 2 was 0.99, and the proportion of tumor cells determined by RT-PCR was 4 times greater than in MFC data (fig. 1). Summary/Conclusion:On 36 day, the greatest concordance of MRD results was observed, probably due to low clearance of tumor cells. However, on 70 and 133 days, negative results were often observed by MFC while BCR-ABL1 transcripts persisted. This could happen due to persistence of BCL-ABL1 transcript in non-leukemic cells or due to higher sensitivity of RT-PCR. This conclusion may improve the predictive ability of the MRD tests in the prospective studies.
Background:Acute lymphoblastic leukemia (ALL) is a rare disease in adults. Despite the novels therapies, clinical outcomes remain unsatisfactory. Bone marrow allograft still holds its place as a consolidation treatment for patients in complete remission in order to improve the prognosis and lengthen survival.Aims:We study in this work the feasibility and outcome of bone marrow allograft for adult Philadelphia chromosome negative ALL.Methods:Our study is retrospective including the cases of high‐risk adult ALL (HR) diagnosed in the hematology department of Hédi Chaker Hospital of Sfax during the period from January 2004 to December 2015. These patients were treated according to protocols inspired by GRAALL 2003 and 2005. The indication of bone marrow allograft is systematic in patients whose age are <50 years and having a compatible intrafamilial donor. For our patients we studied the allograft indication, the search for a family compatible HLA donor, the feasibility of the allograft and finally the result of this one which was carried out at the national center of bone marrow transplantation in Tunis.Results:Among the 36 cases of adult phi negative ALL treated with the GRAALL 2003 and 2005 protocols, 28 patients were in complete remission (CR) and 22 patients (79%) were classified as HR. Twenty patients had indication of bone marrow allograft (2 were> 50 years of age). Of the 20 patients who had an HLA study, 14 patients (70%) had a compatible HLA family donor. Allogeneic bone marrow allograft could only be performed for 9 patients: 64% of patients with a compatible HLA donor and 45% of patients with CR. For the 5 others the transplant could not be done for: relapsed before allograft for 2 cases and severe comorbidities for the 3 others. The median time to completion of the allograft was 15 weeks. Among the allografts, 6 patients (67%) were living in CR after a follow‐up of 74 months, one patient relapsed at 6 months post‐transplant and 2 patients died of acute GVH. Of the 19 non‐allograft CR patients, 6 patients were living in CR (31%) and 1 died during consolidation therapy and 12 relapsed. The 5‐year DFS of both allografted and non‐allografted patients was 72% and 21%, respectively.Summary/Conclusion:Despite the cost‐effectiveness of the intra‐familial HLA study (70% donor) in our study, allografting could only be performed for a small number of patients (45%), hence the need to expand the indication of allograft for subjects over 50 years old or perform a mini allograft, do the same haplo transplant and even expand donor sources on files (pheno‐identical donors). Two‐thirds of the allografted patients in our series did not relapse, an interesting result and comparable to the literature.
Background:Childhood acute myeloid leukemia (AML) represents 20% of childhood acute leukemia. Despite major improvement in outcome, the prognostic is pejorative compared with childhood acute lymphoblastic leukemia.Aims:We report the clinical features and treatment outcome of children de novo AML in southern Tunisia.Methods:Our study is retrospective including Children (age ≤ 20 years) affected by de novo AML between January 2005 and June 2018 treated in the department of hematology of CHU Hedi Chaker Sfax. Diagnosis has been established according to FAB classification confirmed by flow cytometry. Secondary leukemia and FAB M3 were excluded. Induction chemotherapy associated cytarabine 200 mg/m2 for 7 days and daunorubicin 60 mg/m2 for 3 days or mitoxantrone 12 mg/m2 for 5 days. After induction, patients with an HLA‐matched sibling donor underwent allogeneic Bone Marrow Transplantation (allo‐BMT) in first complete remission (CR1). Patients without a matched sibling donor received in CR1 three or four courses of consolidation. We evaluated complete remission rate, overall survival (OS) and event‐free survival (EFS). The Kaplan‐Meier method was used to estimate OS and EFS.Results:We collected 52 cases of childhood AML, including 28 boys and 24 girls (sex ratio = 1.03). The median age at diagnosis was 12 years (1.5‐20 years). The median initial white blood cell and hemoglobin level were 76 G/L (extreme 0.9 G/L ‐ 900 G/L) and 6.5 g / dL respectively. The median count of platelet was 55000/mm3. Distribution according FAB classification was: 17% of AML0, 21% of AML1, 19% of AML2, 23% of AML4, 6%of AML5 and 2% of AML6, 6% of AML7 and 2% of AMLbipheno. Cytogenetic of bone marrow cells showed chromosomal abnormalities in 58% of cases, only 13 (25%) patients had favorable abnormalities. Thirty‐one patients (60%) achieved complete response after one cure and 34 patients (65 %) after one or two courses of chemotherapy. Failure rate and toxic death were respectively 8% and 27%. Hematopoietic stem cell transplant was indicated in 24 (46%) patients but only 8 underwent the procedure. Nine patients (17.3%) relapsed within 8 months from diagnosis. The 5‐year OS and EFS were 50% and 48% respectively.Summary/Conclusion:Our study is characterized by frequent leucocytosis forms and FAB type M2. The CR rate and our EFS and OS rates observed in our series remain lower than in international trials. These can be explained by the frequency of refractory forms and the small number of bone marrow transplantation. Intensification chemotherapy of induction as well as consolidation therapy with allo‐BMT can improve the outcome of our patients.
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