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A comprehensive analysis of 220 patients diagnosed with APL between 1993 and 2022 is here reported. Overall, 214 patients (97.2%) received induction therapy. Complete response (CR) was achieved in 97.4%, 100%, 100%, and 27% of patients treated with AIDA protocol, AIDA + Ara-C, ATRA + ATO, and ATRA monotherapy, respectively. Molecular complete response (CRMRD-) was achieved in 96.8% cases, and 142 patients proceeded to maintenance therapy. Overall, the 3-year and 5-year overall survival (OS) rates were 80.8% (95% CI, 78.1–83.5) and 79.1% (95% CI, 76.4–81.8), respectively. Considering only patients who completed induction and maintenance therapy, the 5-year OS rates were 82.1% (95% CI, 77.5–86.7) for the AIDA0493 cohort, 87.5% (95% CI, 84.4–91.1) for the AIDA2000 cohort, and 100% for the APL0406 cohort (p = 0.044). Additionally, the disease-free survival (DFS) rates were 65.7% (95% CI, 60.4–70.9), 70% (95% CI, 65.8–75.2), and 95.1% (95% CI, 91.7–98.5) (p = 0.016), respectively. Among low and intermediate-risk patients, age > 70 years (p = 0.027) and relapse (p < 0.001) were significantly associated with reduced outcomes. This study contributes to the advancement of our understanding of APL treatment, underscoring the ongoing need for research to enhance outcomes and explore new therapeutic approaches and prognostic factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Relapses of acute promyelocytic leukemia (APL) remain a challenge despite the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Given the variability in salvage therapies and emerging evidence supporting the deferral of hematopoietic cell transplantation (HCT) in patients receiving ATO, we analyzed the outcomes of a multicentric cohort of 67 relapsed APL patients. Better outcomes were reported with ATO ± ATRA compared to chemo-based regimens and ATRA ± Gemtuzumab ozogamicin (GO). A significant survival advantage was observed for patients undergoing HCT in the chemo-based cohort (p = 0.017), but not in the ATO-based group (p = 0.12). Achieving molecular complete remission (CR) post salvage therapy emerged as the main prognostic factor for second relapses in both univariate and multivariate analyses. Our findings support the efficacy of ATO-based therapies in first relapse and enhance the role of molecular remission as an independent outcome predictor in both first and second APL relapses. Background: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes. Methods: A retrospective analysis was performed on a multicentric cohort of 67 APL patients in first relapse, treated in three Italian hematology centers from June 1981 to November 2021. The overall survival (OS) and cumulative incidence of relapse (CIR) were calculated, and predictive factors were assessed using Cox regression models. Results: Overall, 61 patients (91%) received ATO ± ATRA (40.3%), chemo-based regimens (40.3%), or ATRA ± Gemtuzumab ozogamicin (GO) (10.4%). Complete remission (CR) was achieved in 98.2% of patients (molecular CR, n = 71.4%). With a median follow-up time of 54.5 months, the 5-year OS was 73% in the ATO ± ATRA group, 44% in the chemo-based group, and 29% in the ATRA ± GO group (p = 0.035). The 5-year OS rate was also higher for transplant recipients vs. non-recipients within the chemo-based cohort (50% vs. 33%, p = 0.017), but not in the ATO-based cohort (p = 0.12). ATO-based salvage therapy resulted in better OS in both univariate (p = 0.025) and multivariate analyses (p = 0.026). The 2-year CIR was higher in patients without molecular CR vs. patients in molecular CR (66% vs. 24%, p = 0.034). Molecular CR was a significant predictor of second relapse in both univariate (p = 0.035) and multivariate analyses (p = 0.036). Conclusions: Our findings support the efficacy of ATO-based therapies in first relapse of APL and confirm the achievement of molecular remission as an independent outcome predictor in both first and second APL relapse. [ABSTRACT FROM AUTHOR]

Simple Summary: FLT3 mutations are common in acute myeloid leukemia (AML) and are often associated with poorer outcomes and higher relapse rates. This study examined the long-term outcomes of FLT3-mutated (FLT3m) AML patients who received intensive treatment at our institution over the past 24 years, comparing the results in patients who received standard chemotherapy alone with those who received a FLT3 inhibitor (FLT3i). Our single-center, real-life experience confirms the impact of FLT3i administration on survival, both in frontline and salvage settings. In addition, our results underline that the proper positioning of allogeneic stem cell transplantation in the therapeutic algorithm is still an unmet need. These findings suggest that incorporating FLT3-targeting agents into treatment plans may improve outcomes for AML patients while highlighting the need for the continued optimization of treatment strategies to enhance patient survival and quality of life. We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 109/L, and 52% had an NPM1 co-mutation. Until 2018, 101 patients received chemotherapy; thereafter, 39 received 3+7+midostaurin. The overall CR rate was 64%, higher in NPM1 mutant patients (73%). Univariate analysis showed that NPM1 mutation (p = 0.032) and WBC < 100 × 109/L (p = 0.013) positively influenced the response, with a trend for FLT3i administration (p = 0.052). Multivariate analysis confirmed WBC count as an independent prognostic factor (p = 0.017). In CR1, 41/90 patients underwent allogeneic and 18 autologous transplantation. The median EFS was 1.1 vs. 1.6 years in autografted and allografted patients, respectively (p = 0.9). The one-year non-relapse mortality was 0.00% for autologous and 28% for allogeneic transplants (p = 0.007); CIR at 1 and 3 years was higher in autologous transplants (39% vs. 15% and 57% vs. 21%, p = 0.004). The median survival was not reached in the FLT3i group. Overall, 69 patients received stem cell transplantation (18 autologous, 51 allogeneic). Post-transplant FLT3i was resumed in eight patients, all alive after a median of 65 months. Allogeneic transplantation is crucial in FLT3-mutated AML, but the next challenge will be to identify which patients can benefit from transplants in CR1 and in which to intensify post-transplant therapy. [ABSTRACT FROM AUTHOR]

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990–1999) to 46% (2015–2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies. [ABSTRACT FROM AUTHOR]

Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury due to microvascular platelet-rich thrombi. iTTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (vWF)-cleaving protease, due to anti-ADAMTS13 autoantibodies. Early diagnosis and treatment reduce the mortality. Frontline therapy includes daily plasma exchange (PEX) with fresh frozen plasma replacement and immunosuppression with corticosteroids. Caplacizumab has recently been added to frontline therapy. Caplacizumab is a nanobody that binds to the A1 domain of vWF, blocking the interaction of ultra-large vWF multimers with the platelet and thereby preventing the formation of platelet-rich thrombi. Caplacizumab reduces mortality due to ischemic events, refractoriness, and exacerbations after PEX discontinuation. Until now, the criteria for response to treatment mainly took into account the normalization of platelet count and discontinuation of PEX; with the use of caplacizumab leading to rapid normalization of platelet count, it has been necessary to redefine the response criteria, taking into account also the underlying autoimmune disease. Monitoring of ADAMTS13 activity is important to identify cases with a low value of activity (<10IU/L), requiring the optimization of immunosuppressive therapy with the addition of Rituximab. Rituximab is effective in patients with refractory disease or relapsing disease. Currently, the use of Rituximab has expanded, both in frontline treatment and during follow-up, as a pre-emptive approach. Some patients do not achieve ADAMTS13 remission following the acute phase despite steroids and rituximab treatment, requiring an individualized immunosuppressive approach to prevent clinical relapse. In iTTP, there is an increased risk of venous thrombotic events (VTEs) as well as arterial thrombotic events, and most occur after platelet normalization. Until now, there has been no consensus on the use of pharmacological thromboprophylaxis in patients on caplacizumab because the drug is known to increase bleeding risk. [ABSTRACT FROM AUTHOR]

Gemtuzumab ozogamicin (GO), is an anti-CD33 monoclonal antibody, approved for AML CD33 + , those patients with low and intermediate-risk who obtain a complete response may also be candidated for consolidation with autologous stem cell transplantation (ASCT). However, there are scant data on the mobilization of hemopoietic stem cells (HSC) after fractionated GO. We retrospectively studied data from five Italian centers and identified 20 patients (median age 54 years, range 29–69, 15 female, 15 NPM1mutated) that attempted HSC mobilization after fractionated doses of GO + "7 + 3" regimen and 1–2 cycles of consolidation (GO + HDAC + daunorubicin). After chemotherapy and standard G-CSF, 11/20 patients (55%) reached the threshold of 20 CD34 + /µL, and HSC were successfully harvested, while 9 patients (45%) failed. The median day of apheresis was Day + 26 from the start of chemotherapy (range 22–39 days). In good mobilizer patients, the median circulating CD34 + cells were 35.9 cells/µL and the median CD34 + harvested were 4.65 × 106/kg of patients' body weight. With a median follow-up of 12.7 months, at 24 months from the first diagnosis, 93.3% of all 20 patients were alive and the median overall survival was 25 months. The 2-year RFS rate from the timepoint of the first CR was 72.6%, while the median RFS was not reached. However, only five patients underwent ASCT and achieved full engraftment. In conclusion, in our cohort of patients, the addition of GO reduced HSC mobilization and harvesting, which was reached in about 55% of patients. Nevertheless, further studies are warranted to evaluate the effects of fractionated doses of GO on HSC mobilization and ASCT outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the benefits and safety of the empiric antibiotic treatment (EAT) active against KPC-K. pneumoniae in febrile neutropenic patients with acute leukaemia (AL) who are colonised by KPC-K. pneumoniae. Patients and Methods: A 7-year (2013– 2019) retrospective observational cohort study was conducted at the Haematology, Sapienza Rome University (Italy) on 94 febrile neutropenia episodes (FNE) in AL patients KPC-K. pneumoniae carriers treated with active EAT. Results: Eighty-two (87%) FNE were empirically treated with antibiotic combinations [38 colistin-based and 44 ceftazidime-avibactam (CAZAVI)-based], 12 with CAZAVI monotherapy. Successful outcomes were observed in 88/94 (94%) FNE, 46/49 (94%) microbiologically documented infections, and 24/27 (89%) gram-negative bloodstream infections (GNB-BSI). Mortality due to infective causes was 4.2% (2.1% within 1 week). KPC-K. pneumoniae infections caused 28/94 FNE (30%) and KPC-K. pneumoniae-BSI was documented in 22 FNE (23.4%) (85% of GNB-BSI), in all cases patients received active EAT, and 21 survived. KPC-K.pneumoniae-BSI mortality rate was 4.5%. CAZAVI-based EAT showed better results than colistin-based EAT (55/56 vs 33/38, p = 0.037), overall and without EAT modification (41/56 vs 20/38, p = 0.02). Empirical combinations including CAZAVI were successful in 98% of cases (43/44 vs 33/38 for colistin-based EAT, p = 0.01), without modifications in 82% (36/44 vs 20/28, p = 0.02). All deaths occurred in patients treated with colistin-based EAT (4/38 vs 0/56, p = 0.02). CAZAVI-containing EAT was the only independent factor for an overall successful response (HR 0.058, CI 0.013– 1.072, p = 0.058). Nephrotoxicity occurred in 3(8%) patients undergoing colistin-based EAT (none in those undergoing CAZAVI-based EAT, p = 0.02). Conclusion: KPC-K. pneumoniae infections are frequent in colonised AL patients with FNE. EAT with active antibiotics, mainly CAZAVI-based combinations, was effective, safe, and associated with low overall and KPC-K. pneumoniae-BSI-related mortality. [ABSTRACT FROM AUTHOR]

COVID-19 disease has a strong impact on hematological patients; those receiving autologous hematopoietic stem cell transplantation (aHSCT) represent a particularly vulnerable group, in which the effectiveness of vaccination is very variable. Chiarucci et al. showed that patients affected by non-Hodgkin lymphoma (NHL) and treated with rituximab experienced a lower rate of immunization against SARS-CoV-2 (54%), as well as significantly lower IgG antibody titers. In our multicenter retrospective observational study, we included 82 patients who underwent aHSCT, divided into two groups: 58 patients vaccinated after aHSCT (group A) and 24 vaccinated before getting transplantation (group B). In group A, 39 (67%) patients had positive serology, and the rate of positivity increased with time after aHSCT. In the subgroup of patients with NHL, the administration of rituximab predicted negative serology, particularly when administered in the 6 months before vaccination (13% response rate). Patients affected by plasma cells had a higher rate of positivity (83% overall), independently of the time to aHSCT. In group B, no patient who initially showed positive serology became negative after transplantation, so the aHSCT did not affect the response to the vaccination. Our study confirmed the role of rituximab as a negative predictor of response to SARS-CoV-2 vaccination, whereas the conditioning and transplantation procedure itself seemed to be less important. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) has gained growing consideration as a treatment option for favorable-risk acute myeloid leukemia (FR-AML) in first complete remission (CR1), compared with chemotherapy. Materials and Methods: We report the long-term outcomes of 117 consecutive patients with FR-AML fit for intensive chemotherapy diagnosed in our center between 1999 and 2020, who underwent ASCT. Results: Sixty-five of the 117 were eligible for intensive post-remission treatment, and 42 of those 65 received ASCT. Median follow up was 132 months. Overall survival (OS) and disease-free survival (DFS) were 75% and 76%. Higher doses of CD34 + stem cell infusions negatively impacted DFS in multivariate analysis. Core-binding factor (CBF) leukemia was an independent prognostic factor for improved DFS. No differences based on pre-transplant measurable residual disease (MRD) were observed. In CBF leukemia, 10-year DFS is 72% for MRD-positive patients versus 100% for MRD negative patients. Conclusions: ASCT is effective and safe in FR-AML patients. In CBF leukemia, ASCT provides excellent results regardless of achievement of bone marrow MRD negativity. In NPM1-mutated/FLT3-wild type (mNPM1) AML, early molecular response seems to have more impact on prognosis. Prospective investigation of the role of gemtuzumab ozogamicin in this setting is ongoing. [ABSTRACT FROM AUTHOR]

Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. Methods: This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma. Eighty-one patients participated. Results: Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. Conclusion: NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT. [ABSTRACT FROM AUTHOR]

The past three decades have brought major therapeutic advances in treating acute promyelocytic leukemia (APL) both in adults and children. The current state-of-the-art treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in combination or not with chemotherapy results in long-lasting remission and cure in more than 90% of newly diagnosed patients. These treatments have made relapse a rare event. The detection of PML-RARA transcript by polymerase chain reaction (PCR) during treatment and follow-up can predict a hematological relapse. All studies have suggested a survival benefit in patients with molecular relapse given pre-emptive therapy compared with those treated at the time of overt hematological relapse. ATO-based regimens seem to be effective for achieving a second molecular complete remission (CR). Patients in second molecular CR are generally considered candidates for autologous hematopoietic stem cell transplant (HSCT), while for those with a persistent molecular disease, allogeneic HSCT should be offered if a suitable donor is identified. Except for sporadic pediatric reports, most of the evidence for using HSCT to treat relapsed/refractory APL comes from adult literature. Therefore, we now provide a review of published pediatric data that evaluated the role of HSCT in children with refractory/recurrent APL disease. [ABSTRACT FROM AUTHOR]

Management of patients with concomitant acute lymphoblastic leukemia (ALL) and COVID-19 infection is challenging. We describe the clinical history of a 40-year-old male with relapsed B-common ALL who developed Sars-CoV2 prior to treatment initiation with inotuzumab. Since the patient was asymptomatic for COVID-19, the first dose of inotuzumab was administered, followed by remdesivir as prophylaxis. However, a worsening in respiratory findings led to a delay in administering the following doses of inotuzumab. Interestingly, even if the patient did not receive the full inotuzumab cycle, he achieved a complete hematologic remission: furthermore, he spontaneously developed anti-sars-COV2 antibodies. COVID-19 treatment also included convalescent plasma, leading to negativization of the viral load. The patient, after COVID-19 recovery, received a second full cycle of inotuzumab, underwent allogeneic transplantation, and is currently in complete hematologic and molecular remission, in good clinical conditions, five months from allograft. [ABSTRACT FROM AUTHOR]

Myeloid sarcoma (MS) is a very rare disease in both adults and children. Prognosis is poor in adults; in the pediatric age, the prognostic impact of extramedullary disease is controversial. Systemic therapy represents the mainstay of treatment even in isolated MS, but a comparison between different induction regimens is very limited in the literature. To date, it is still not clear if induction treatment should differ from that of other acute myeloid leukemias and stem cell transplant is considered for consolidation in both leukemic patients and in those with isolated disease. Our study describes a retrospective series of 13 cases of MS (adults and children), diagnosed and treated at our institute over 18 years. We report the results of immunophenotypic, cytogenetic and molecular studies, therapeutic approaches, and outcome, in order to establish the best strategy for patients' workup. [ABSTRACT FROM AUTHOR]

Background: Acquired Haemophilia A (AHA) patients show a high response rate to immunosuppressive therapy (IST) but few information about predictors of response and outcome are reported. Aims: We describe a large single‐centre AHA cohort, investigating prognostic variables for the 'best response' (BR), time to BR (TTBR) and overall survival (OS). Methods: A total of 61 patients were included, collecting data from clinical charts. Results: A progressive increase in diagnoses, from 1978 to 2019, was observed. Fifty/56 patients (89%) underwent haemostatic therapy (rFVIIa 46%, aPCC 34%) with no significant differences in the response (rFVIIa 92.3% vs aPCC 100%) and no thromboembolic events. Sixty/61 patients underwent first‐line IST with an initial response rate of 58.4%. The 12‐months OS was 85%, the bleeding associated mortality rate 3% (2/61). The response rates at last observation were: CR 64%, PR 8%. We evaluated the influence of age, gender, associated conditions, IST, haemoglobin levels, FVIII:C, inhibitor titre on BR, TTBR and OS: post‐partum AHA achieved the BR after a longer time than AHA related to other aetiologies or idiopathic (p =.05); in univariate analysis female sex (p =.03) and the achievement of BR (p =.001) had a positive impact on the OS while AHA secondary to neoplasms showed a shorter survival (p =.04); only the BR achievement remained significant in multivariate analysis (p =.02). Conclusions: Our data on response and survival confirmed those from the main registries. Post‐partum AHA and BR achievement were significantly associated to a longer TTBR and a longer OS, respectively. Other predictors of outcome deserve to be explored in prospective studies. [ABSTRACT FROM AUTHOR]

Background: KPC-K.pneumoniae bloodstream infection (KPC-KpBSI) mortality rate in patients with hematological malignancies is reported about 60%. The initial treatment active against KPC-K.pneumoniae is crucial for survival and KPC-K.pneumoniae rectal colonization usually precedes KPC-KpBSI. We evaluated the impact on KPC-KpBSI mortality of the preemptive use of antibiotics active against KPC-K.pneumoniae, as opposed to inactive or standard empiric antibiotics, for the empiric treatment of febrile neutropenia episodes in patients with hematological malignancy identified as KPC-K.pneumoniae intestinal carriers.Methods: We compared the outcomes of KPC-KpBSIs occurring in high-risk hematological patients known to be colonized with KPC-K.pneumoniae, during two time periods: March2012-December2013 (Period 1, initial approach to KPC-K.pneumoniae spread) and January2017-October2018 (Period 2, full application of the preemptive strategy). The relative importance of the various prognostic factors that could influence death rates were assessed by forward stepwise logistic regression models.Results: KPC-KpBSI-related mortality in hematological patients identified as KPC-K.pneumoniae carriers dropped from 50% in Period 1 to 6% in Period 2 (p < 0.01), from 58 to 9% in acute myeloid leukemia carriers(p < 0.01). KPC-KpBSIs developed in patients identified as KPC-K.pneumoniae carriers were initially treated with active therapy in 56% and 100% of cases in Period 1 and Period 2, respectively (p < 0.01), in particular with an active antibiotic combination in 39 and 94% of cases, respectively(p < 0.01). The 61% of KPC-KpBSI observed in Period 1 developed during inactive systemic antibiotic treatment (none in Period 2, p < 0.01), fatal in the 73% of cases. Overall, KPC-KpBSI-related mortality was 88% with no initial active treatment, 11.5% with at least one initial active antibiotic (p < 0.01), 9% with initial active combination. Only the initial active treatment resulted independently associated with survival.Conclusions: In high-risk hematological patients colonized by KPC-K.pneumoniae, the empiric treatment of febrile neutropenia active against KPC-K.pneumoniae reduced KPC-KpBSI-related mortality to 6% and prevented fatal KPC-KpBSI occurrence during inactive systemic antibiotic treatment. [ABSTRACT FROM AUTHOR]

P9 showed a different molecular profile, I FLT3-TKD+/NPM1 i + at diagnosis and I FLT3/TKD i and I NPM1 i wild type at relapse; however, at relapse the patient presented as myeloid sarcoma of the skin. At diagnosis, this patient received intensive chemotherapy followed by PBSCT; at relapse, he was treated with high dose cytarabine plus intrathecal therapy followed by an allogeneic transplant. The occurrence of an acute myeloid leukemia (AML) relapse is generally observed within 2-3 years after complete remission (CR) and affects the overall survival rate of these patients [[1]]. Aim of our study was to evaluate, in a large series of AML patients diagnosed at our Center, the incidence of very late AML relapses, in addition, the therapeutic strategies and the outcome of these patients. [Extracted from the article]

Despite advances in understanding the pathogenesis of acute myeloid leukemia (AML), the standard therapy remained nearly unchanged for several decades. There have been many efforts to improve the response and survival by either increasing the cytarabine (ARA-C) dose or adding a third agent to the standard chemotherapy regimen. Several studies have evaluated the addition of cladribine (CdA) to standard induction, exploiting its property to potentiate ARA-C uptake. Response rates for combination regimens including CdA in relapsed/refractory (R/R) adults are approximately 50% and approximately 70% in de novo AML. Recently, a low intensity combination of CdA and ARA‐C alternating with decitabine has shown promising results in older patients with AML. In this review, we will discuss the role of CdA in the treatment of AML, summarizing the recent clinical data regarding its incorporation into the induction therapy for adult AML. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is a potential consolidation therapy for acute myeloid leukemia (AML). This study was designed to develop a prediction model for leukemia-free survival (LFS) in a cohort of patients with de novo AML treated with ASCT during their first complete remission.Methods: This was a registry study of 956 patients reported to the European Society for Blood and Marrow Transplantation. The primary outcome was LFS. Multivariate Cox regression modeling with backward selection was used to select variables for the construction of the nomogram. The nomogram's performance was evaluated with discrimination (the area under the receiver operating characteristic curve [AUC]) and calibration.Results: Age and cytogenetic risk (with or without FMS-like tyrosine kinase 3 internal tandem duplication) were predictive of LFS and were used for the construction of the nomogram. Each factor in the nomogram was ascribed points according to its predictive weight. Through the calculation of the total score, the probability of LFS at 1, 3, and 5 years for each patient could be estimated. The discrimination of the nomogram, measured as the AUC, was 0.632 (95% confidence interval [CI], 0.595-0.669), 0.670 (95% CI, 0.635-0.705), and 0.687 (95% CI, 0.650-0.724), respectively. Further validation with bootstrapping showed similar AUCs (0.629 [95% CI, 0.597-0.657], 0.667 [95% CI, 0.633-0.699], and 0.679 [95% CI, 0.647-0.712], respectively), and this suggested that the model was not overfitted. Calibration was excellent. Patients were stratified into 4 incremental 5-year prognostic groups, with the probabilities of LFS and overall survival ranging from 25% to 64% and from 33% to 79%, respectively.Conclusions: The Auto-AML nomogram score is a tool integrating individual prognostic factors to provide a probabilistic estimation of LFS after ASCT for patients with AML. [ABSTRACT FROM AUTHOR]

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low-risk karyotype (P < .001), no high-risk karyotype (P = .006), positivity for AML-ETO (P = .004)/CBFβ-MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3-ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 109 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 109 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) spread and infections in patients with haematological malignancies are a serious concern especially in endemic areas. Treatment failures and delay in appropriate therapy for CRKP infections are frequent and the mortality rate associated with CRKP bacteremia in neutropenic haematological patients is reported about 60%.Methods: Haematological patients harboring CRKP hospitalized between February 2012 and May 2013 in an Italian Teaching hospital were examined. Conditions favouring CRKP spread in a haematological unit, risk factors for bacteremia in CRKP-carriers and for CRKP bacteremia-related death were evaluated in this observational retrospective study.Results: CRKP was isolated in 22 patients, 14 (64%) had bacteremia. Control measures implementation, particularly the weekly rectal screening for CRKP performed in all hospitalized patients and contact precautions for CRKP-carriers and newly admitted patients until proved CRKP-negative, reduced significantly the CRKP spread (14 new carriers identified of 131 screened patients vs 5 of 242 after the intervention, p = 0.001). Fifty-eight percent of carriers developed CRKP bacteremia, and acute myeloid leukemia (AML) resulted independently associated with the bacteremia occurrence (p = 0.02). CRKP bacteremias developed mainly during neutropenia (86%) and in CRKP-carriers (79%). CRKP bacteremias were breakthrough in 10 cases (71%). Ten of 14 patient with CRKP bacteremias died (71%) and all had AML. The 70% of fatal bacteremias occurred in patients not yet recognized as CRKP-carriers and 80% were breakthrough. Initial adequate antibiotic therapy resulted the only independent factor able to protect against death (p = 0.02).Conclusions: The identification of CRKP-carriers is confirmed critical to prevent CRKP spread. AML patients colonized by CRKP resulted at high risk of CRKP-bacteremia and poor outcome and the adequacy of the initial antibiotic therapy may be effective to improve survival. To limit the increase of resistance, the extensive use of antibiotics active against CRKP should be avoided, but in the setting of high CRKP pressure and high-risk CRKP-colonized haematological patients, timely empiric antibiotic combinations active against CRKP could be suggested as treatment of febrile neutropenia. [ABSTRACT FROM AUTHOR]

Congenital afibrinogenemia (CA) is a disease characterized by a complex pathophysiology, involving both the procoagulant and fibrinolytic systems, as well as platelet activity. Although hemorrhagic diathesis represents the most frequent clinical presentation of this disorder, severe thrombotic events can occur. It is not yet clear if these events are strictly related to the disease itself or to the fibrinogen replacement therapy. Different hypotheses on the pathophysiological mechanisms have been proposed. It is well known that fibrinogen/fibrin has a role in the downregulation of thrombin generation in plasma. In the absence of circulating fibrinogen, this "antithrombin" activity is missing and plasma thrombin levels rise; this excess of thrombin could promote clotting of the infused fibrinogen, initiating the thrombotic process. Furthermore, the observation of impaired plasmin generation in the plasma of CA patients has raised the hypothesis of a fibrinolytic system deficiency. We report the case of a CA male patient who at the age of 36 years experienced an arterial thrombosis in his left lower limb. Despite an aggressive medical treatment with low-molecular-weight heparin, fibrinolytic and antiplatelet agents, the arterial thrombosis progressed to the obstruction of the whole left arterial district and the patient underwent the amputation of the left lower limb. This case demonstrates the complexity of pathophysiology and clinical management of a "so- called" bleeding disorder as CA. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the role of pre-transplant minimal residual disease (MRD) negativity in a consecutive cohort of high-risk acute lymphoblastic leukemia (ALL) patients treated between 1996 and 2015. Topics discussed include details and high-risk features of the patients, eligibility of the patients for an autologous stem cell transplant (ASCT), and importance of detecting and quantifying MRD in predicting the outcome of ALL.

Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy. [ABSTRACT FROM AUTHOR]

Purpose: The use of peripherally inserted central catheters (PICC) as an alternative to other central venous access devices (CVAD) is becoming very frequent in cancer patients. To evaluate the impact of complications associated to these devices in patients with hematologic malignancies, we revised the catheter-related bloodstream infections (CRBSI) and the catheter-related thrombotic complications (CRTC) observed at our institute between January 2009 and December 2012.Methods: A total of 612 PICCs were inserted into 483 patients at diagnosis or in subsequent phases of their hematologic disease. PICCs were successfully inserted in all cases. The median duration of in situ PICC placement was 101 days (interquartile range, 48-184 days).Results: A CRBSI occurred in 47 cases (7.7 %), with a rate of 0.59 per 1000 PICC days. A CRTC was recorded in 16 cases (2.6 %), with a rate of 0.20 per 1000 PICC days. No serious complication was associated to these events. Cox regression analyses of variables associated to CRBSIs and to CRTCs showed that only the type of disease (acute leukemia compared to other diseases) was significantly associated to a higher incidence of CRBSIs, while no feature was predictive for a higher risk of CRTCs.Conclusions: PICCs represent a useful and safe alternative to conventional CVAD for the management of patients with hematologic malignancies. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case study of a 30-year-old Caucasian female who had an isolated ovarian relapse after undergoing an allogeneic stem cell transplant for the treatment of acute lymphoblastic leukemia.

Long-term survival of relapsed/refractory acute myeloid leukemia (AML) remains a major problem, particularly in patients not eligible for transplantation. We hereby evaluated the feasibility and efficacy of adding Gemtuzumab Ozogamicin to salvage chemotherapy (Ara-C, Idarubicine, Peg-Filgrastim) in relapsed/refractory AML. The main end points were: the rate of complete remissions (CR) and the proportion of patients capable of undergoing a stem cell transplant. Fourty-two patients were enrolled. The overall CR rate was 76% and no induction deaths were reported. In 56% of patients, a transplant procedure could be performed. The treatment schedule proved feasible and well tolerated, providing a high CR rate and a useful bridge to transplant. [ABSTRACT FROM AUTHOR]

Introduction: Systemic Epstein-Barr-virus-positive T cell lymphoproliferative disease of childhood is an extremely rare disorder, characterized by clonal proliferation of Epstein-Barr-virus-infected T cells with an activated cytotoxic phenotype. The disease is more frequent in Asia and South America, with only few cases reported in Western countries. A prompt diagnosis, though often difficult, is a necessity due to the very aggressive clinical course of the disease.Case Presentation: We report the clinicopathological features of fulminant T cell lymphoproliferative disease that arose in the setting of acute primary Epstein-Barr virus infection. Our patient, a 23-year-old man, presented to our facility with persisting fever, hepatosplenomegaly and severe pancytopenia. On bone marrow biopsy, an abundant lymphoid infiltrate was observed. Immunophenotypic and molecular studies revealed that the atypical lymphoid cells displayed a CD8+, Epstein-Barr-encoded-RNA-positive T cell phenotype with clonal rearrangement of the T cell receptor genes, the final diagnosis being systemic Epstein-Barr-virus-positive T cell lymphoproliferative disease. On reviewing the literature we found only 14 similar cases, all presenting with very aggressive clinical courses and requiring extensive phenotyping and molecular techniques for final diagnosis.Conclusion: Though extremely rare, this disease can occur in Europe, and a comprehensive diagnostic approach is thus recommended in all case of Epstein-Barr-virus-positive lymphoproliferative disorders. Unfortunately, at present no specific treatment is available; however, prompt administration of anti- Epstein-Barr virus treatment and rapid attempts to control the hemophagocytic syndrome are indicated. [ABSTRACT FROM AUTHOR]

Little is known about the incidence and clinical impact of cytomegalovirus (CMV) infection in patients with acute myeloid leukemia at the time of diagnosis and during chemotherapy. The aims of the present study were to assess prospectively the incidence of active CMV infection in 69 consecutive patients with acute myeloid leukemia and to describe the outcomes of treatment. pp65 antigenemia was monitored at diagnosis, post-induction and post-consolidation chemotherapy, and whenever CMV reactivation was suspected. Patients with pp65 antigenemia received pre-emptive anti-CMV treatment. Fifty-nine patients achieved complete remission. Baseline CMV serology results were available for 56 of the 59 patients: 52 patients (93%) were IgG positive. The overall incidence of pp65 antigenemia in patients in complete remission after chemotherapy was 35% (21/59): 9 patients after induction and 12 post-consolidation. Sixteen of the 21 pp65-positive patients received anti-CMV treatment: 15 as pre-emptive therapy and 1 for interstitial CMV pneumonitis. Five patients received no anti-CMV treatment and did not develop CMV disease. Patients with pp65 antigenemia had more hospital admissions (2.57 vs. 2.16; P = 0.009), while patients with >10 pp65-positive cells had more clinical complications (8/9 vs. 2/12; P = 0.002). In conclusion, patients with acute myeloid leukemia receiving chemotherapy should be monitored for active CMV infection. CMV reactivation in these patients was associated with an increased number of hospital admissions, and high levels of pp65 antigenemia were associated with more clinical complications. Controlled studies are needed to assess the relevance of pre-emptive anti-CMV therapy in patients with acute myeloid leukemia receiving chemotherapy. J. Med. Virol. 82: 1201-1207, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Since 1997, 32 newly diagnosed multiple myeloma patients responsive to DAV chemotherapy were autografted with idarubicin-intensified busulphan-melphalan (ida-bu-mel). Main endpoints of the study were transplant-related toxicity, overall survival (OS) and progression-free survival (PFS). The results were compared with a historical control group of 38 patients treated with the ‘standard’ bu-mel regimen. Concerning time to engraftment, no significant difference was observed between the two groups, while toxicity was significantly higher in the intensive conditioning group, regarding grade IV mucositis, duration of profound neutropenia, incidence of infections and platelet requirement. Five-year OS and PFS are 73 versus 78% and 37 versus 48% for the intensive and standard regimen, respectively (p value not significant). The ida-bu-mel schedule appears to be a feasible and effective regimen for newly diagnosed multiple myeloma patients; nevertheless, no apparent benefit in OS and PFS arises from the comparison with a historical control treated with standard bu-mel, which is better tolerated and at least equally effective. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bone marrow transplantation (BMT) is a sophisticated procedure consisting of the administration of high-dose chemoradiotherapy followed by intravenous infusion of hemopoietic stem cells to reestablish marrow function when bone marrow is damaged or defective. BMT is used in the treatment of solid tumors, hematologic diseases, and autoimmune disorders. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing BMT to minimize the nutritional consequences of both the conditioning regimens (eg, mucositis of the gastrointestinal tract) and complications resulting from the procedure (eg, graft versus host disease and venoocclusive disease of the liver). Although artificial nutrition is now recognized as the standard of care for BMT patients, defined guidelines for the use of artificial nutrition in this clinical setting are lacking. During the past 2 decades, artificial nutrition in BMT patients has moved from simple supportive care to adjunctive therapy because of the possible benefits, not strictly nutritional, of specialized nutritional intervention. Although data exist documenting the beneficial role of special nutrients, such as lipids and glutamine, in the management of BMT recipients, the results obtained to date are controversial. The reasons for this controversy may reside in the heterogeneity of the patients studied and of the study designs. This review focuses on the need to J correctly identify the different patterns of BMT to achieve reproducible and reliable data, which may in turn be used to devise precise guidelines for the use of specialized artificial nutrition in BMT patients [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the occurrence of thrombotic thrombocytopenic purpura during the first trimester of pregnancy and at the time of delivery or during the post-partum period.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30–50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23); heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (β −3.34, 95%CI −6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy. [ABSTRACT FROM AUTHOR]