Catálogo de publicaciones - revistas

<jats:title>Abstract</jats:title><jats:p>Multi‐parametric flow cytometry (MFC) has a well‐established role in measurable residual disease (MRD) monitoring in patients with B‐lymphoblastic leukemia (B‐ALL). However, the optimal time‐point (TP) for early MRD testing and associated prognostic impact remain undefined in adult B‐ALL patients receiving Hyper‐CVAD induction chemotherapy. To evaluate the utility of MRD analysis after one cycle (TP1) in comparison to MRD analysis after two cycles (TP2) of induction treatment with Hyper‐CVAD chemotherapy, we studied 49 adult B‐ALL patients over a 10‐year period (2010–2020) who had available bone marrow samples for morphological and MFC MRD assessments at the two separate TPs. Median times to TP1 and TP2 relative to start of treatment were 21 and 45 days, respectively. When censored at transplant, achievement of MRD negativity at TP1 was not associated with a statistically significant improvement in either event‐free survival (EFS) (<jats:italic>p</jats:italic> = .426) or overall survival (OS) (<jats:italic>p</jats:italic> = .335) when compared to patients with MRD positivity. In contrast, achieving MRD negativity at TP2 was associated with a statistically significant improvement in both EFS (<jats:italic>p</jats:italic> = ·005) and OS (<jats:italic>p</jats:italic> = .047) over patients who remained MRD positive. Multivariate analysis demonstrated that <jats:italic>KMT2A</jats:italic>‐rearrangement and MRD positivity at TP2 were the only significant predictors of outcome, correlating with worse EFS and OS. Therefore, in the absence of residual morphologic disease, MRD analysis after one cycle of Hyper‐CVAD induction chemotherapy did not provide additional benefit with regard to risk stratification or correlation with survival outcomes when compared to MRD testing after two cycles of Hyper‐CVAD in adult B‐ALL patients.</jats:p>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction and Objectives</jats:title><jats:p>Lenalidomide is considered a standard of care in multiple myeloma (MM) Some MM patients will develop delayed hypersensitivity to lenalidomide, which can lead to treatment discontinuation. Desensitization to lenalidomide can help these patients to complete treatment courses. Here, we aimed to review lenalidomide‐treated MM patients who developed delayed hypersensitivity‐induced rash and were treated with desensitization.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A retrospective analysis of medical files of MM patients, who were desensitized to lenalidomide due to delayed hypersensitivity rash. Patients were treated between 2018 and 2022 at Hadassah Medical Center, Jerusalem, Israel.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Search of patients yielded 16 patients that underwent desensitization to lenalidomide within the study period. The desensitization protocol consisted of a slow, 3‐week‐long protocol with lenalidomide's target doses of 10, 15, and 25 mg/day. Of the 16 patients, 10 (62.5%) succeeded to complete the protocol and thus were able to complete lenalidomide treatment cycles. One patient with unsuccessful desensitization was subsequently treated with first‐generation IMiD thalidomide, with no rash appearing. None of the patients that were treated with desensitization had severe immune‐mediated or non‐dermatological adverse reactions.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Desensitization to lenalidomide is safe and effective. Discontinuation of lenalidomide in MM patients with delayed hypersensitivity and no contraindication to desensitization should be discouraged. Collaboration between hematologists and allergists is needed.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>Aim of the study was to evaluate the role of a Domiciliary Hematologic Care Unit (DHCU) compared to standard DH setting in the active frontline treatment with hypomethylating agents (HMAs) +/− venetoclax of frail patients with acute myelogenous leukemia/high‐risk myelodysplastic syndromes (AML/HR‐MDS).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>All patients with newly diagnosed AML/HR‐MDS unfit for intensive care and treated frontline with HMAs from January 2010 to April 2021 were retrospectively included.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 112 patients (62 AML/50 HR‐MDS), 69 (61.6%) were treated in a standard DH setting and 43 (38.4%) were followed by DHCU, allocated to DH or DHCU by responsible physician. Overall response rate was 29/69 (42.0%) in DH versus 19/43 (44.1%) in DHCU (<jats:italic>p</jats:italic> = .797). Median response duration was 8.7 months (95%CI 7.0–10.3) in DH versus 13.0 months (95%CI 8.3–17.6) in DHCU (<jats:italic>p</jats:italic> = .460). Infections were also equally reported. Median overall survival of patients treated in DH was 13.7 months (95%CI 9.9–17.4) compared to 13.0 months (95%CI 6.7–19.3) of patients managed by DHCU (<jats:italic>p</jats:italic> = .753).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Home care management of HMA is feasible and effective, with results similar to standard DH setting: this approach is thus adequate to offer active therapies in frail patients with AML/HR‐MDS considered up to now ineligible.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>To compare cyclosporine (CSA) combining eltrombopag (EPAG) with or without antithymocyte globulin (ATG) in aplastic anemia (AA) patients in the real world.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>AA patients who received ATG combining CSA and EPAG (Group A) and CSA + EPAG (Group B) as front‐line treatment in 13 medical centers in China were enrolled. The efficacy and safety were compared.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 89 patients were enrolled with 51 patients in Group A and 38 patients in Group B. The 6‐month overall response (OR)/complete response (CR) was 73.3%/24.4% and 60.6%/27.3% in Groups A and B (<jats:italic>p</jats:italic> &gt; .1). For severe AA patients, the 6‐month OR was 74.1% versus 50% and 6‐month CR was 25.9% versus 20% in Groups A and B (<jats:italic>p</jats:italic> &gt; 0.1). Multivariate analysis showed gender affects the 6‐month OR with females better OR (<jats:italic>p</jats:italic> = .017, OR 6.045, 95% CI: 1.377–26.546) and time from disease onset to treatment affected the 12‐month CR (<jats:italic>p</jats:italic> = .026, OR 0.263, 95% CI: 0.081–0.852). No difference was found in side effects except ATG infusion reaction and serum sickness. Mortality was 7.8% in Group A and no patient died in Group B.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>CSA + EPAG had a similar response and less side effects compared with standard immunosuppressive therapy + EPAG in newly diagnosed AA.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Telomere biology diseases (TBD) result from defective telomere maintenance, leading to bone marrow failure. The only curative treatment for aplastic anemia related to TBD is a hematopoietic cell transplant (HCT). Although reduced‐intensity conditioning (RIC) regimens decrease transplant‐related mortality, non‐hematological phenotypes represent a major challenge and are associated with poor long‐term follow‐up outcomes.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To describe the outcome of TBD patients transplanted for marrow failure.</jats:p></jats:sec><jats:sec><jats:title>Study Design</jats:title><jats:p>This is a retrospective, single‐center study describing the outcomes of 32 consecutive transplants on 29 patients between 1993 and 2019.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The median age at transplantation was 14 years (range, 3–30 years). Most patients received a RIC regimen (<jats:italic>n</jats:italic> = 28) and bone marrow (BM) from an unrelated donor (<jats:italic>n</jats:italic> = 16). Four patients received a haploidentical transplant. Chimerism was available for 27 patients with a median time to neutrophil recovery of 20 days (13–36 days). Primary graft failure occurred in one patient, whereas second graft failure occurred in two. Acute GVHD grade II‐IV and moderate to severe chronic GVHD occurred in 22% of patients at risk. Fourteen patients were alive after HCT at the last follow‐up (median, 6 years; 1.4–19 years). The 5‐year overall survival was better after matched sibling donor (MSD) transplantation compared to other hematopoietic stem cell sources (88.9% vs. 47.7%; <jats:italic>p</jats:italic> = .05; CI = 95%). Overall, 15 patients died after HCT, most of them (<jats:italic>n</jats:italic> = 11) after the first year of transplant, due to non‐hematological disease progression or complication of chronic GVHD.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Hematopoietic cell transplantation is a potentially curative treatment option for TBD, nonetheless the poor outcome reflects the progression of non‐hematologic disease manifestations, which should be considered when transplantation is indicated.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporin A is the standard treatment for aplastic anemia (AA). However, the efficacy of repeated IST with rabbit ATG (rATG) as salvage therapy remains unclear in patients with relapsed or refractory AA.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We retrospectively evaluated the efficacy and safety of IST2 with rATG (IST2‐rATG) in 19 consecutive patients with relapsed or refractory AA who received first‐line IST with rATG in two centers between 2009 and 2020.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The overall 6‐month response rate of the patients was 58%. The response rates were similar between patients with relapsed and refractory AA. The presence of glycophosphatidylinositol‐deficient blood cells was associated with a better response to IST2‐rATG. Despite retreatment with the same rATG, serum disease and severe allergic reactions were not observed.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>IST2‐rATG is effective and safe for the treatment of adult patients with relapsed and refractory AA after receiving first‐line IST with rATG.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid β‐glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8–10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists.</jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p>This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level &lt; 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count &lt;100.000/mm<jats:sup>3</jats:sup>) in 24 (5.5%).</jats:p><jats:p>Of 600 MGUS patients tested for acid β‐glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, <jats:italic>GBA</jats:italic> gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease.</jats:p></jats:sec>