Prognostic Value of Minimal Residual Disease (MRD) Detection in Adult Acute Lymphoblastic Leukemia (ALL) – HYPER-CVAD Protocol

Abstract

Objective: HYPER-CVAD is an intensive treatment protocol of short duration, for ALL and other lymphoid neoplasms. It is consisted of 8 alternating cycles (parts A and B): in part A (cycles 1, 3, 5, 7) fractionated doses of cyclophosphamide, vincristine, doxorubicin and dexamethazone are administrated, while in part B (cycles 2, 4, 6, 8) high doses of methotrexate and aracytin. The two first cycles compose the induction therapy, while the next 6 cycles constitute the consolidation therapy, followed by two years of maintenance therapy. Protection of CNS is achieved with intradorsal injections, whereas in Ph+ ALL patients, imatinib is also administered. The aim of this study was the clinical evaluation of MRD detection in adult patients with ALL, during chemotherapy with HYPER-CVAD. Patients/Methods: During the period 1999–2008, 30 patients were hospitalized in our hospital for ALL and were treated with HYPER-CVAD therapeutic protocol. Among them, 14/30 (46,7%) were males and 16/30 (53,3%) females (median age 43,5 years, range 16–70). Median follow-up time was 12,8 months (range 0,5–100). ALL of T-origin had 8/30 patients and of B-origin, 22/30 (1 B1-EGIL/pro-B, 17 B2-EGIL/B-common, 4 B3-EGIL/pre-B). Caryotypic analysis and FISH was done in all patients (7/30 bcr/abl+). According to classical prognostic markers of ALL: 21/30 were classified as high, 4/30 as medium and 5/30 low risk, respectively. MRD presence was detected in bone marrow samples, with flow cytometric panels, at three particular treatment time-points: completion of induction therapy (T1), completion of consolidation therapy (T2) and at the end of maintenance therapy (T3). Overall survival (OS) and disease free survival (DFS) were investigated, especially in relation to the influence of MRD presence in (OS) and (DFS), respectively. For statistical analysis, Kaplan-Meier was used. Results: At treatment time-point (T1), MRD was detected in 10/28 (35,7%) patients, at time-point (T2) in 7/23 (30,4%) and at treatment-point (T3) in 9/17 (52,94%). The influence of MRD detection in (OS) was statistically significant (p<0,05) at (T2) and (T3), while in (DFS) the detection of MRD presence in any of the standardized treatment time-points resulted in decreased DFS (T1/p<0,05, T2 and T3/p<0,001). Conclusions: Our results suggest that MRD detection during therapy of adult ALL is a negative prognostic indicator for (OS) and (DFS), the independency of which has to be confirmed after prolonged follow-up time and increased number of cases.

Multicenter analysis of outcomes in blastic plasmacytoid dendritic cell neoplasm offers a pretargeted therapy benchmark

“…It is interesting that, despite the expression of typical lymphoid markers such as CD4 and TdT, the somatic mutations in BPDCN are more typical for myeloid malignancies. [34][35][36] However, our findings, similar to those reported by others, 29,37,38 suggest that patients who receive lymphoid-type chemotherapy regimens may experience better outcomes. Our cohort was not powered to determine if lymphoid marker expression correlated with response to lymphoid-type therapy.…”

Blastic plasmacytoid dendritic cell neoplasms: results of an international survey on 398 adult patients

“…8 Eligible patients should be considered for allo-HSCT consolidation in first CR whenever feasible. However, these patients represent the minority of BPDCN patients, because the disease normally affects elderly patients, with a median age of 68 years, 9 which is also very close to the median age in our study (67 years), resulting in only 15.5% who received allo-HSCT. On the other hand, patients not eligible for transplant could benefit more from intensive induction regimens that are considered to be more effective compared with standard therapies (eg, CHOPlike).…”

“…In selected patients, the use of chemotherapy followed by allo-HSCT and, to a lesser extent, auto-HSCT, was associated with significantly better outcomes. 8,9,12,13,[23][24][25][26] On the other hand, in view of the retrospective nature of our study, we were not able to determine with absolute certainty the rationale for clinical decisions when allocating treatment strategy. However, it is plausible that autografted patients in our study were deemed ineligible for an allo-HSCT as a result of advanced age or associated comorbidities.…”

“…[5][6][7] BPDCN has a poor prognosis, in part because it commonly displays early drug resistance against conventional cytotoxic agents. The use of AML-like, acute lymphoblastic leukemia (ALL)-type, or non-Hodgkin lymphoma (NHL)-like chemotherapy regimens is associated with a complete remission (CR) rate of 40% to 90% [8][9][10] ; however remissions are usually short-lived, resulting in a median overall survival (OS) of 12 to 14 months [9][10][11] Patients who received an allogeneic hematopoietic stem cell transplant (allo-HSCT) had better survival results compared with those who received chemotherapy alone (median OS, 22.7 months vs 7.1 months; P 5 .03). 5 In a retrospective study from the European Society for Blood and Marrow Transplantation, when feasible, allo-HSCT was associated with a 3-year OS of 41%, reaching 53% in patients who were transplanted in first CR.…”