Summary
In the European LeukemiaNet favourable risk category, allogeneic haematopoietic stem cell transplantation (alloSCT) is not indicated in first complete remission for patients with acute ...myeloid leukaemia (AML) with NPM1 mutations (ELNfav NPM1 AML), although a proportion of these patients will relapse. Given the prognostic importance of measurable residual disease (MRD), CETLAM‐12 considered a pre‐emptive intervention in patients with molecular failure (MF). We analyzed 110 ELNfav NPM1 AML patients achieving complete remission (CR) after induction chemotherapy. Two‐year cumulative incidence of relapse (CIR), overall survival (OS) and leukaemia‐free survival (LFS) were 17%, 81·5% and 82%, respectively. Forty‐six patients required additional therapy for MF (n = 33) or haematological relapse (HemR; n = 13), resulting in a molecular LFS (molLFS) and a cumulative incidence of MF at two years of 61% and 38% respectively. Two‐year OS for these 46 patients was 66%, with a different outcome between patients with MF (86%) and HemR (42%) (P = 0·002). Quantitative NPM1 detection at different timepoints was predictive of molLFS; an MRD ratio (NPM1mut/ABL1 × 100) cut‐off of 0·05 after first consolidation identified two cohorts with a two‐year molLFS of 77% and 40% for patients below and above 0·05, respectively. In conclusion, MRD‐based pre‐emptive intervention resulted in a favourable outcome for ELNfav NPM1 AML patients.
Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat ...AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5′‐nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate‐risk cytogenetic AML patients receiving cytarabine‐based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p: .003; HR 2.16, 95% CI 1.29–3.61) and lower disease‐free survival (DFS) (p: .002; HR 2.45, 95% CI 1.41–4.27), associated to a higher relapse incidence (p: .010; HR 2.23, 95% CI 1.21–4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT‐3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment.
We present the first case reported of Cytomegalovirus (CMV) infection in adrenal gland (AG) diagnosed by Endoscopic Ultrasound. Moreover, it is a rare case of unilateral CMV infection of AG in a ...non-HIV infected patient mimicking a neoplasic hypercaptation in PET. Case Report: A 71-year-old woman with stage IV follicular lymphoma in complete remission since 2006. In March 2019, chemotherapy treatment was initiated due to a relapse with pulmonary involvement. At three months, the patient presented bad general condition and fever. A positron emission tomography (PET) showed abnormal metabolic activity in the left adrenal gland (AG) suggestive of lymphoma recurrence. Tuberculosis and human immunodeficiency virus (HIV) infection were ruled out. Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) was performed. A hypoechoic, heterogeneous nodular lesion, with well-defined margins, about 27x16mm of maximum diameters was reported. Cytopathology confirmed isolated epithelial cells without cytological atypia, focus of adrenal adenoma, and cytomegalic inclusions with positive immunohistochemical expression for cytomegalovirus (CMV). A clinical improvement was observed after treatment with ganciclovir. Discussion: The most frequent causes of solid unilateral lesions in AG in patients without HIV infection are benign lesions such as adenomas, primary malignancy tumors and metastases of lung neoplasia. AG infections secondary to CMV typically occur HIV-infected patients and with bilateral involvement. The presence of an adenoma in left AG could have caused a false-positive in initial PET, but after ganciclovir treatment, no abnormal metabolic activity was detected in control PET. To our knowledge, this is the first case reported in the literature of unilateral CMV infection of AG in a non-HIV infected that have been diagnosed by EUS-FNA. Given that PET scan hypercaptation is not always diagnostic of malignancy, it is mandatory to obtain pathological samples, of which EUS-FNA has proven the best technique.
Objective and methods
Pediatric‐inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent ...modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T‐cell ALL. We analyzed 169 patients with high‐risk T‐cell ALL included in two consecutive trials of the PETHEMA Group (HR‐ALL03 n = 104 and the more contemporary HR‐ALL11 n = 65).
Results
Patients and disease characteristics were balanced between both groups. Regarding efficacy, we observed a similar complete remission (CR) rate, relapse and disease‐free survival (DFS) between both protocols. Patients included in the HR‐ALL11 trial had better 2‐year overall survival (OS) compared with the HR‐ALL03 (65% 95% CI 51%‐79% vs 44% 95% CI 34%‐54%, P = 0.026). Regarding toxicity, we observed a better safety profile in the HR‐11 protocol. Irrespective of the protocol, patients with good measurable residual disease (MRD) clearance had a promising outcome without allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in CR1, with 2‐year OS of 67%.
Conclusion
Patients with T‐cell ALL included in the HR‐11 trial showed better OS than patients in the HR‐03, mostly driven by a reduction of NRM.
The use of rituximab together with intensive chemotherapy in Burkitt's lymphoma or leukemia (BL) has been scarcely explored. This study prospectively evaluated and compared the outcome and toxicity ...of human immunodeficiency virus (HIV)-positive and HIV-negative patients with BL who were treated in an intensive immunochemotherapy-based and age-adapted trial.
A total of 118 adult patients (80 HIV-negative and 38 HIV-positive) aged 15 to 83 years were treated with 4 (nonbulky stages I-II) or 6 (stages II bulky, III-IV) cycles of intensive chemotherapy combined with rituximab. Reduction in chemotherapy doses and modification of the cycle schedules was performed in patients older than 55 years.
The clinical characteristics of HIV-positive patients were comparable with those who were HIV-negative. Complete remission rates were 82% and 87%, respectively, and 9 patients died in induction, 9 died in remission, and 7 relapsed. After a median follow-up of 2.5 years, nonsignificant differences were observed in the 4-year disease-free survival and overall survival (OS) probabilities (77% and 63% for HIV-positive and 80% and 78% for HIV-negative patients, respectively). Young HIV-infected patients presented higher incidences of grade 3 or 4 mucositis and severe infectious episodes. Poor general status and bone marrow involvement, but not advanced age, were associated with a shorter OS, allowing the definition of 3 prognostic groups, with the OS ranging from 50% to 92%.
Age-adapted intensive immunochemotherapy is highly effective in both HIV-negative and HIV-positive patients, with a higher toxicity in the latter group. Poor general status and bone marrow involvement had a negative impact on survival.
Introduction
Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.
Objective
The aim of this ...study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.
Methods
In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.
Results
Sixty‐one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One‐ and 4‐year CIR were 52% and 56%. One‐ and 4‐year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).
Conclusion
Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.
High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, ...toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).
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