Cytomegalovirus and ClostridiumDifficile co-infection in severe ulcero-hemorrhagic colitis during inductionchemotherapy for acute lymphoblastic leukemia

Here we describe the first case of a biopsyprovenCytomegalovirus ulcero-hemorrhagic colitis,associated with Clostridium Difficile co-infection,occurring during standard induction chemotherapyfor common B cell acute lymphoblastic leukemia.We discuss the case and focalize clinical managementand diagnostic issues arising from it

Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia

Recent genomic studies have identified a wide range of novel genetic alterations that have substantially increased our knowledge of the biology of B- and T-progenitor acute lymphoblastic leukaemia (B-ALL, T-ALL) and defined new subtypes with prognostic and therapeutic relevance.1-4 Thanks to the use of transcriptome sequencing approaches, new cryptic fusion transcripts have been described, such as the ATP5L-KMT2A gene fusion, described by Gestrich et al. in a 14-month-old patient with aggressive B-ALL.5 ATP5L or ATP5MG (ATP Synthase Membrane Subunit G) catalyzes ATP synthesis during oxidative phosphorylation.6 This protein has recently been reported to interact with a SARS-CoV-2 protein.7 The histone lysine [K]-methyl transferase 2A (KMT2A) gene is a transcriptional coactivator that plays an essential role in regulating gene expression during early development and haematopoiesis. It is frequently rearranged to over 135 translocation partner genes in acute leukaemias.8 ATP5L is a novel KMT2A fusion partner not detectable by fluorescent in situ hybridization (FISH) or karyotype, due to the closeness of the two genes on chromosome 11q23. The Cleveland Medical Centre team found a reciprocal out-of-frame ATP5L-KMT2A rearrangement that juxtaposes the ATP5L exon 1 to the KMT2A exon 2, with the insertion of an extra nucleotide (G) at the fusion site.5 We sequenced leukaemic cells from eight adult ALL patients (two T-ALL, five B-ALL Philadelphia negative (Ph−) and one B-ALL Ph+; Table I) by a 199 gene RNA-sequencing panel (RNA-seq; Pan-Heme FusionPlex, ArcherDx Inc., Boulder, CO, USA).The study was supported by European Union Seventh Framework Programme (FP7/2007-2013) (GA 306242-NGS-PTL) and Associazione Italiana Leucemie (AIL)

Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study

Background: Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy. Methods: We describe 71 R/R B-ALL patients treated for different relapses with Blina and InO. Blina was the first treatment in 57 patients and InO in 14. Twenty-seven patients had a previous allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: In the Blina/InO group, after Blina, 36 patients (63%) achieved a complete remission (CR), with 42% of negative minimal residual disease (MRD−); after InO, a CR was achieved in 47 patients (82%, 34 MRD−). In the InO/Blina group, after InO, 13 cases (93%) reached a CR (6 MRD−); after Blina, a CR was re-achieved in 6 cases (43%, 3 MRD−). Twenty-six patients proceeded to allo-HSCT. In the Blina/InO group, the median overall survival (OS) was 19 months; the disease-free survival (DFS) after Blina was 7.4 months (11.6 vs. 2.7 months in MRD− vs. MRD+, p = 0.03) and after InO, 5.4 months. In the InO/Blina group, the median OS was 9.4 months; the median DFS after InO was 5.1 months and 1.5 months after Blina (8.7 vs. 2.5 months in MRD− vs. MRD+, p = 0.02). With a median follow-up of 16.5 months from the start of immunotherapy, 24 patients (34%) are alive and 16 (22%) are alive in CR. Conclusion: In our series of R/R B-ALL, Blina and InO treatment demonstrate efficacy for subsequent relapses in terms of MRD response, OS and DFS, and as a bridge to allo-HSCT

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse-< 12 months from diagnosis-was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p = <0.001), hyperleucocytosis >100 × 109 /L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible

Anagrelide in Essential Thrombocythemia: A Retrospective Analysis of 220 Patients. Session Type: Poster Session 646-III

This retrospective study analyses 220 patients with Essential Thrombocythemia (ET) treated with Anagrelide in 26 Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC). The patients, 81 males and 139 females, at diagnosis had a mean age of 39 years (13-40 years 55%; 41-60 years 35%; 61-82 years 10%) and showed a mean PLT count (109/L) of 1108, previous thrombosis (4.5%), previous hemorrhage (3%), disease related symptoms (20%), cardiovascular risk factors (32%) and splenomegaly (25%). At start of Anagrelide treatment the mean PLT count (109/L) was 907 (>1000 in 32%). The 68% of patients were receiving an antiplatelet treatment and the 74% received cytoreductive drugs (Alkylating agents and HU 17%, HU alone 20%, HU and IFN 21%, IFN alone 16%). The treatment with Anagrelide was started mainly because of the young age of patients, inefficacy and/or high dose required, toxicity and/or side effects of the other drugs and patient request. The mean daily Anagrelide dose from the baseline of 1.3 mg was increased to 1.5 mg after 1 month and to 1.8 mg since the 12th month. The most common side effects were cephalea/vertigo (24%), palpitation/tachycardia (24%), gastrointestinal (9%), asthenia (8%), oedema (5%). A transitory interruption of Anagrelide treatment was observed in 44/220 cases (20%) as a consequence of drug toxicity (3.7%), side effects (5%), no drug availability (4.5%), other causes (6.8%). A drug withdrawal was registered in 54/220 patients (24.5%) after a median treatment duration of 17 months when the mean Anagrelide dose was 1.8 mg/day and the mean PLT count was 665 x109/L), because of inefficacy (3%), toxicity (3%), side effects (9.5%), compliance loss (1%), no drug availability (3%),other causes (5%). The mean follow-up of all 220 patients was 21 months. The mean PLT count (109/L) from the baseline value of 907 decreased to 586, 505, 490, 458 and 449 after 1, 6, 12, 36 and 60 months, respectively. The mean WBC count (109/L) was 7.7 at the baseline and 9.2 after 60 months. The mean Hb level (g/dL) from the baseline of 13.2 decreased to 12.8 and 12.4 at months 6 and 60, respectively. Two minor hemorrhagic events (0.51/100 pt-yrs) and 3 major thrombotic events (0.77/100 pt-yrs) were observed during the follow-up. In this series of ET patients the treatment with the non-mutagenic Anagrelide has been confirmed to be effective and globally well tolerated. Nevertheless, new prospective studies are necessary to define the Anagrelide long-term toxicity, particularly in terms of thrombotic and/or hemorrhagic complications and anemia occurrence