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In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality–infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01–0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality.

Progressive multifocal leukoencephalopathy (PML) is a rare, subacute demyelinating disorder of the central nervous system (CNS) caused by the JCV. In immunosuppressed hosts, PML is caused by reactivation of a latent infection rather than primary exposure. Hematological patients, particularly post-transplant, presenting with worsening neurological symptoms should promptly consider PML in the differential diagnosis. The rarity of PML after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and the absence of a universally effective therapy represents a clinical challenge. Here, we present two cases of PML developed after autologous and allogeneic HSCT, with completely different outcomes dependent on the patients’ clinical backgrounds and the level of immune system competence which is the key factor in determining either the onset or viral clearance of the infection.

The text reports the clinical case of a 61-year-old woman with a long history of generalized pruritus who was eventually diagnosed with T-cell prolymphocytic leukemia (T-PLL), a rare and aggressive T-cell lymphoproliferative disorder. At presentation, the patient had fever, skin lesions, lymphocytosis, thrombocytopenia, coagulation abnormalities, and marked splenomegaly without lymphadenopathy. Morphological, immunophenotypic, and histological analyses of peripheral blood and bone marrow revealed diffuse infiltration by mature T lymphocytes with strong TCL1 expression, and T-cell receptor gene rearrangement confirmed clonality, supporting the diagnosis of T-PLL. The patient initially received bendamustine chemotherapy, which failed to induce a response. Second-line treatment with the anti-CD52 monoclonal antibody alemtuzumab was subsequently initiated, but the disease proved refractory, with persistent bone marrow involvement, worsening cytopenias, disease progression, and clinical deterioration. As a result, alemtuzumab was discontinued and the patient was transitioned to palliative care. A particularly notable finding was the detection, by next-generation sequencing, of a pathogenic KRAS G12A mutation, which has not previously been reported in T-PLL. This mutation was identified incidentally using a myeloid-targeted NGS panel. The finding broadens the known mutational spectrum of T-PLL and suggests that activation of the RAS signaling pathway may represent an alternative oncogenic mechanism beyond the canonical TCL1 and JAK–STAT pathways. We suggest that investigating for KRAS mutations in additional T-PLL cases may be beneficial to explore this pathogenetic pathway and could open new avenues for future targeted therapeutic strategies.

Abstract 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.

Promyelocytic blast crisis (BC) of CML is an extremely rare event, with only seven cases described as arising during therapy with TKIs. We present a 68-year-old male who developed promyelocytic blast crisis 12 months after CML diagnosis and start of Imatinib therapy, confirmed by the concomitant presence of the t(15;17) and t(9;22) translocations in the leukemic cells. Molecular remission for the PML-RARA clone was achieved with standard acute promyelocytic leukemia induction therapy with ATRA and idarubicin. However, BCR-ABL showed resistance to first-line Dasatinib and second-line Ponatinib, principally due to the presence of multiple mutations in ABL1 kinase domain, including T315I. Hematological and molecular response was achieved with Asciminib, a first‐in‐class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor in combination with pulsed ATRA as post-remission strategy. Of the 7 cases of promyelocytic BC reported in the era of TKI therapy for CML, this is the first case effectively treated with Asciminib therapy.

A real-life study on CPX-351 and the standard arm (‘7 + 3’) of the CPX-351 registrative trial in adults with secondary Acute Myeloid Leukemia were compared by an unanchored Matching-adjusted indirect comparison (MAIC), in order to evaluate the efficacy and toxicity of CPX-351. Results of this study are important to confirm the role of CPX-351 in significantly improving survival and remission rates compared with ‘7 + 3’ with a good safety profile in AML patients with high-risk features, a target group traditionally with a very poor prognosis. Moreover, this pilot analysis underlines the potentiality of the statistical method to compare studies with strong differences.

We retrospectively studied a consecutive series of 100 patients with acute leukemia and aspergillosis to evaluate the clinical findings and risk factors for colonization of the central nervous system (CNS) by Aspergillus species. The diagnosis of CNS aspergillosis was made in 14 patients on the basis of the following criteria: neurological signs of CNS involvement (13 of 14 patients); cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and histological findings at autopsy (11 of 11). The majority of patients had severe neurological complications (i,e., hemiparesis or seizures), due mainly to brain abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and provided evidence that CNS localization was secondary to invasive aspergillosis; in each case, the most likely primary focus of infection was the lung. Although all patients had received oral antimycotic prophylaxis and had received timely empirical antifungal treatment, they all died within a median time of 5 days from the onset of neurological symptoms. Analysis of the characteristics of patients with invasive aspergillosis did not reveal any difference between those with CNS localization and those without eNS localization.

Molecular follow-up has been carried out using immunoglobulin heavy-chain (IgH) gene finger-printing, a polymerase chain reaction (PCR)-based technique with a sensitivity of 0.1-0.01% (10(-3)-10(-4)), in 22 patients affected by multiple myeloma and submitted to stem cell transplantation (SCT). Twelve patients were submitted to either single or double autologous unselected peripheral blood progenitor cell transplantation, eight patients were submitted to autologous CD34+ immunoselected transplantation and two patients were submitted to allogeneic bone marrow (one patient) or peripheral blood CD34+ stem cell (one patient) transplantation. At diagnosis, all patients showed clonal CDIII rearrangement. The molecular analysis performed on leukapheresis products and CD34+ purified fractions proved to be contaminated by myeloma cells. During follow-up after autografting, all but one patient retained clonal rearrangement despite clinical complete remission (CR) in ten of them. These ten patients either relapsed (Rel) or showed progressive disease (PD) after transplantation; four of them died. Only one patient did not retain clonal rearrangement after autologous transplantation; she is currently alive in CR after a follow-up of 100 months. One patient submitted to allogeneic transplantation is currently alive with no evidence of the disease, but still retains clonal rearrangement after a follow-up of 47 months. Another patient died 4 months after transplantation after succumbing to fatal pneumonia showing myeloma progression.