Prospective study on the impact of BEAM versus FEAM conditioning on occurrence of neutropenic enterocolitis and on transplant outcome in lymphoma patients.

Introduction: Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM). Neutropenic enterocolitis (NEC) is a life-threatening complication occurring after intestinal mucosa damage related to intensive chemotherapy. NEC mortality may be up to 30%-50%. In our study, we compared NEC incidence, symptoms, mortality, and transplant outcome in terms of overall survival (OS) and progression-free survival (PFS) in the BEAM vs. FEAM groups. Furthermore, we compared the cost of hospitalization of patients who did vs. patients who did not experience a NEC episode (NECe). Methods: A total of 191 patients were enrolled in this study (N = 129 and N = 62 were conditioned with BEAM and FEAM, respectively). All patients received bed-side high-resolution ultrasound (US) for NEC diagnosis. Results and discussion: NEC incidence and NEC-related mortality were similar in the BEAM and FEAM groups (31% and 40.3%, p = 0.653, and 5% and 8%, p = 0.627, respectively). At a median follow-up of 116 months, no difference was noted between BEAM vs. FEAM groups in terms of OS and PFS (p = 0.181 and p = 0.978, respectively). BEAM appeared equivalent to FEAM in terms of NEC incidence and efficacy. The high incidence of NEC and the low mortality is related to a timely US diagnosis and prompt treatment. US knowledge in NEC diagnosis allows to have comparable days of hospitalization of patients NECpos vs. patients NECneg. The cost analysis of NECpos vs. NECneg has been also performed.

Impact of different chemotherapy regimens on intestinal mucosal injury assessed with bedside ultrasound: a study in 213 AML patients.

Introduction: Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage. Methods: In our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN). Results and discussion: Overall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening.

Early Diagnosis of Neutropenic Enterocolitis by Bedside Ultrasound in Hematological Malignancies: A Prospective Study.

(1) Background: Neutropenic enterocolitis (NEC) is a life-threatening complication following chemotherapy with high mortality rates. Early diagnosis is crucial to improve outcomes. We designed a large prospective study employing bedside ultrasonography (US) as a novel approach to allow early diagnosis and prompt treatment to reduce mortality. (2) Methods: NEC was defined as US or computed tomography (CT)-proven bowel wall thickness ≥ 4 mm at the onset of at least one of the following symptoms: fever and/or abdominal pain and/or diarrhea during neutropenia. From 2007 to 2018, 1754 consecutive patients underwent baseline bedside US that was invariably repeated within 12 h from the onset of symptom(s) suggestive of NEC. (3) Results: Overall, 117 episodes of NEC were observed, and overall mortality was 9.4%. Bowel wall thickening was invariably absent in the negative control group. Abdominal pain associated with one or more symptoms correlated with the highest relative risk (17.33), sensitivity (89.7%), specificity (100%), and accuracy (96.2%) for diagnosis. The combination of abdominal pain and fever at onset significantly correlated with worse survival (p < 0.0001, OR 13.85). BWT (p = 0.046), type of therapy (p = 0.049) and blood culture positivity (p = 0.003) correlated with worse survival. (4) Conclusions: Bedside ultrasound is a non-invasive and radiation free imaging technique for early diagnosis of NEC and its prompt treatment significantly reduced mortality.

Organ Stiffness in the Work-Up of Myelofibrosis and Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

To define the role of spleen stiffness (SS) and liver stiffness (LS) in myelofibrosis and other Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), we studied, by ultrasonography (US) and elastography (ES), 70 consecutive patients with myelofibrosis (MF) (no.43), essential thrombocythemia (ET) (no.10), and polycythemia vera (PV) (no.17). Overall, the median SS was not different between patients with MF and PV (p = 0.9); however, both MF and PV groups had significantly higher SS than the ET group (p = 0.011 and p = 0.035, respectively) and healthy controls (p < 0.0001 and p = 0.002, respectively). In patients with MF, SS values above 40 kPa were significantly associated with worse progression-free survival (PFS) (p = 0.012; HR = 3.2). SS also correlated with the extension of bone marrow fibrosis (BMF) (p < 0.0001). SS was higher in advanced fibrotic stages MF-2, MF-3 (W.H.O. criteria) than in pre-fibrotic/early fibrotic stages (MF-0, MF-1) (p < 0.0001) and PFS was significantly different in the two cohorts, with values of 63% and 85%, respectively (p = 0.038; HR = 2.61). LS significantly differed between the patient cohort with MF and healthy controls (p = 0.001), but not between the patient cohorts with ET and PV and healthy controls (p = 0.999 and p = 0.101, respectively). We can conclude that organ stiffness adds valuable information to the clinical work-up of MPNs and could be employed to define patients at a higher risk of progression.