Anti-HLA donor-specific antibodies in allogeneic stem cell transplantation: management and desensitization protocol

The role of antibodies directed against the human leukocyte antigen (HLA) system has been well analyzed in rejection of solid organ transplantations [1, 2] and in transfusion medicine [3]. In the setting of allogeneic hematopoietic stem cells transplantation (HSCT), only in the recent years their importance has been better defined, even though anti-HLA antibodies are frequently detectable in hematologic patients, due to sensitization from multiple transfusions, usually before the introduction of online universal leukoreduction, previous transplantations, and pregnancies in female patients

Ponatinib induced improvement of cutaneous lesions associated to accelerated phase of Ph-positive chronic myeloid leukemia

Ponatinib a third generation tyrosine kinase inhibitor, has been approved for all phases of disease in CML. In advanced phase, has been confirmed with a good efficacy in all type of resistance, including T315I kinase domain mutation. We here report activity of the drug in advanced phase with extramedullary localization

Prognostic factors associated with a stable MR4.5 achievement in chronic myeloid leukemia patients treated with imatinib

Deep molecular response in chronic myeloid leukemia (CML) patients treated with imatinib is a prerequisite for possible discontinuation. We identify clinico-biologic features linked with the probability of reaching MR4.5 (BCR-ABL/ABL ≤ 0.0032% IS) as a stable response (confirmed on two or more consecutive determinations). In a series of 208 patients treated with imatinib first-line outside clinical trials, after a median follow-up of 7 years the incidence of stable MR4.5 was 34.6%, obtained in median time of 5.4 years. In univariate analysis, female gender (p = 0.02), lower median age (56.4 vs 58.6, p = 0.03), Sokal risk stratification (p = 0.01) and e14a2 type of transcript (43% vs 31%, p = 0.02) are associated to achievement of a stable MR4.5. In multivariate regression analysis, female gender (HR 1.6, 95% CI: 1.1-2.6; P = 0.022), Sokal risk (HR 1.4, 95% CI: 1.1-2.3; p = 0.03), type of transcript (e14a2 vs e13a2 type, HR 1.6, 95% CI: 1.3-2.9; P = 0.03) and achievement of an early molecular response (EMR) at 3 months (HR 1.5, 95% CI: 1.2-2.8; P = 0.01), retained statistical significance. These clinical and biologic features associated with the achievement of a stable deep molecular response should be taken into account at a time when treatment-free remission strategies are being actively pursued in the management of CML

Multiparametric Magnetic Resonance Enterography for the Diagnosis and Staging of Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Background: Intestinal Acute graft-versus-host disease (i-aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). The clinical diagnosis of i-aGVHD is usually based on symptoms and CT findings but a definite diagnosis is made by endoscopic biopsies. To date, there are few data on the use of magnetic resonance enterography (MRE) in this setting. We hereby investigated the value of MRE in the diagnosis of i-aGVHD. Methods: A retrospective observational study was carried out on 35 patients (16 men, 19 women; age 9-69 years) with hematologic malignancies who underwent a MRE for a suspect of i-aGvHD according to the Glucksberg criteria between 2015 and 2017. MRE examinations were performed with a 1.5 Tesla scanner (Siemens, MagnetomAvanto), equipped with 16-channels phased-array coils. We used a protocol including axial and coronal T2-weighted Half Fourier Acquisition Single Shot Turbo Spin Echo sequences, with and without fat saturation; T2 weighted axial and coronal TrueFISP sequences; DWI (Diffusion Weighted Imaging) sequences with b- values of 0, 500 and 1000; axial and coronal T1 weighted VIBE sequences, before and 70 seconds after the intravenous administration of contrast media (0.1 mmol gadolinium per kilogram of body weight, Gd-DOTA, Dotarem®, Guerbet, Aulnays-sous-Bois, France). In adult patients without contraindications, a 10 ml IV dose of hyoscine butylbromide was administered before contrast injection, in order to reduce motion artefacts. To evaluate the presence and severity of the disease, the following parameters were assessed and qualitatively scored for all intestinal segments (from stomach to rectum): a) MRI inflammation-activity including mural T2 signal (oedema), mesenteric T2 signal (oedema), gadolinium wall enhancement on T1 (vascularity), DWI signal (inflammation); b) morphologic parameters of activity and severity, including maximum wall thickness, increased number and/or size of local mesenteric lymph nodes, comb sign (mesenteric vessels dilation), presence of peritoneal effusion. Results: Out of 35 patients, 21 had a definite histologic diagnosis of i-aGVHD while in the remaining 14 patients i-aGVHD was excluded. The above MRE parameters were observed in 19 out of 21(90.5%) patients with a definite diagnosis of i-aGVHD and in none of the 14 patients in which a diagnosis of i-aGVHD was excluded. A stratified mucosal wall enhancement after gadolinium injection was found in 90% of patients. Parietal enhancement was associated with high-grade oedema of mesenteric fat tissue and comb sign in 76% of cases. In 52.4% of cases, mesenteric lymph nodes were not found. Free intra-peritoneal fluid was observed in 57.2% of patients. The most commonly involved intestinal segments were distal ileum (85.7%), mean ileum (66.6%) and proximal ileum (57.1%), followed by ascending colon and sigmoid equally (38%). Spearman's test showed a statistically significant correlation between clinical stage of i- aGVHD and mural T2 signal, number of involved intestinal segments, wall thickness, T1 enhancement, peritoneal effusion (p < .001). Conclusions: In our experience MRE parameters showed a good correlation with a definite i- aGVHD diagnosed and with the stage of disease. Therefore, in patients with a clinical suspect of i-aGVHD MRE examination may be considered in order to replace endoscopic biopsy to confirm the diagnosis

A 35 year single center transplant experience in chronic myeloid leukemia

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has been considered for decades the only curative approach for patients with chronic myeloid leukemia (CML). In the tyrosine kinase inhibitors (TKIs) era, HSCT for CML has been reserved only to patients not achieving a cytogenetic remission or showing progressive disease after multiple TKI treatment lines. However, a progressive improvement in the long-term survival has been obtained in the overall HSCT population. The present study aimed at evaluating whether in CML patients transplanted at our Center over a long time period - from 1983 to 2018 - the outcome improved over time. Methods: 136 consecutive patients who underwent a transplant between 1983 and 1999 were compared to 43 patients who received the transplant between 2000 and 2018. Overall survival (OS), leukemia-free survival (LFS) and graft-leukemia-free survival (GLFS) were estimated using the Kaplan-Meier method and the log-rank test was used to compare risk factors categories. Results: Of the 179 patients [median age 35 years (range7-66)], 148 (82.7%) were in 1st or 2nd chronic phase, 25 (13.9%) in accelerated phase and six (3.4%) in blast crisis. Matched related donors and alternative donors (matched unrelated donors, cord blood or mismatched related donors) were used in 156 and 23 cases, respectively. As stem cell source, bone marrow was used in 142 patients, peripheral blood in 33 and umbilical cord blood in 4. TBI- based conditioning regimens were used in 89 patients, while in the other 90 cases irradiation-free conditioning regimens were used. Both in univariate and multivariate analysis, irradiation- free conditioning regimens (HR 1.8; 95%CI 1.1-3.0, p=.0014) and transplants performed in 1st chronic phase (accelerate phase HR 2.1; 95%CI 1.2-3.8, p=.008 - 2nd chronic phase HR 4.9; 95%CI 2.3-10.3, p=.0001 - blast crisis HR 2.5; 95%CI 1.0-6.4, p< .05) were associated with a better OS. Patients transplanted before 2000 had a worse OS (HR 6.5; 95%CI 2.7-15.5, p < .0001) and DFS (HR 2.2; 95%CI 1.0-4.8, p=.045). A trend for a worse GLFS was observed in univariate analysis (HR 1.6; 95%CI 1.0-2.7, p=0.05), in the first period of observation. Conclusions: Our single center experience confirms that higher OS, DFS and GLFS are observed in CML patients allografted in more recent years. Improvement of con- ditioning regimens, use of TBI-free conditioning regimens and supportive therapy, have presumably contributed to these results, together with the more recent strategy of close monitoring of minimal residual disease, and prompt use of TKI or donor lymphocyte infusion in case of relapse. HSCT is nowadays a safer therapeutic procedure in CML patients that should be considered timely in TKI-resistant patients to avoid progression into a more advanced disease phase. Disclosure: The authors declare no conflict of interest

Pre-emptive use of Sorafenib combined with DLI post HSCT in AML FLT3+: a single center experience

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