Enrico Morello

Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability

Hodgkin lymphoma relapsing after autologous transplantation (autoSCT) has a dismal outcome. Allogeneic transplantation (alloSCT) using reduced intensity conditioning (RIC) is a salvage option, but its effectiveness is still unclear. To evaluate the role of RIC alloSCT, we designed a retrospective study based on the commitment of attending physicians to perform a salvage alloSCT; thus, only Hodgkin lymphoma patients having human leukocyte antigen-typing immediately after the failed autoSCT were included. Of 185 patients, 122 found an identical sibling (55%), a matched unrelated (32%) or a haploidentical sibling (13%) donor; 63 patients did not find any donor. Clinical features of both groups did not differ. Two-year progression-free (PFS) and overall survival (OS) were better in the donor group (39.3% vs 14.2%, and 66% vs 42%, respectively, P < .001) with a median follow-up of 48 months. In multivariable analysis, having a donor was significant for better PFS and OS (P < .001). Patients allografted in complete remission showed a better PFS and OS. This is the largest study comparing RIC alloSCT versus conventional treatment after a failed autoSCT, indicating a survival benefit for patients having a donor.

P. aeruginosa bloodstream infections among hematological patients: an old or new question?

Pseudomonas aeruginosa is a well-known cause of severe and potentially life-threatening infections among hematological patients. A prospective epidemiological surveillance program ongoing at our Hematology Unit revealed an increase over time of P. aeruginosa bloodstream infections (BSI). Their impact on outcome and antibiotic susceptibility was analyzed. BSI which consecutively occurred at our institution during a 70-month period were evaluated and correlated with type of pathogen, status of underlying disease, neutropenia, previous antibiotic therapy, resistance to antibiotics, and outcome. During the observation period, 441 BSI were recorded. Frequency of Gram-negative BSI was higher than that of other pathogens (57.3%). Overall, 66 P. aeruginosa BSI were recorded; 22 out of 66 were multiresistant (MR P. aeruginosa). Thirty-day mortality for all BSI was 11.3%; it was 27.3% for P. aeruginosa BSI and 36.4% for MR P. aeruginosa. At multivariate analysis, only active hematological disease and P. aeruginosa BSI were associated to an increased risk of death. For MR P. aeruginosa, BSI mortality was 83.3% vs. 18.8% when empiric therapy included or not an antibiotic with in vitro activity against P. aeruginosa (p = 0.011). Together with active disease, the emergence of P. aeruginosa BSI, particularly if multiresistant, was responsible for an increased risk of death among hematological patients at our institution. In this scenario, reconsidering the type of combination antibiotic therapy to be used as empiric treatment of neutropenic fever was worthwhile.

Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients

Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q‐PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia‐associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse‐free survival (RFS) were: bone marrow (BM)‐WT1 ≥ 121/104 ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB‐WT1 ≥ 16/104 ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q‐PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk‐adapted, postinduction therapy of AML.

PBSC mobilization in lymphoma patients: analysis of risk factors for collection failure and development of a predictive score based on the kinetics of circulating CD34+ cells and WBC after chemotherapy and G-CSF mobilization

Autologous stem cell transplantation (ASCT) is a potentially curative treatment of lymphoma, but peripheral blood stem cell (PBSC) mobilization fails in some patients. PBSC mobilizing agents have recently been proved to improve the PBSC yield after a prior mobilization failure. Predictive parameters of mobilization failure allowing for a preemptive, more cost‐effective use of such agents during the first mobilization attempt are still poorly defined, particularly during mobilization with chemotherapy + granulocyte colony‐stimulating factor (G‐CSF). We performed a retrospective analysis of a series of lymphoma patients who were candidates for ASCT, to identify factors influencing PBSC mobilization outcome. Premobilization parameters—age, histology, disease status, mobilizing protocol, and previous treatments—as well as white blood cell (WBC) and PBSC kinetics, markers potentially able to predict failure during the ongoing mobilization attempt, were analyzed in 415 consecutive mobilization procedures in 388 patients. We used chemotherapy + G‐CSF in 411 (99%) of mobilization attempts and PBSC collection failed (<2 × 106 CD34+ PBSC/kg) in 13%. Multivariable analysis showed that only a low CD34+ PBSC count and CD34+ PBSC/WBC ratio, together with the use of nonplatinum‐containing chemotherapy, independently predicted mobilization failure. Using these three parameters, we established a scoring system to predict risk of failure during mobilization ranging from 2 to 90%, thus allowing a selective use of a preemptive mobilization policy. Copyright

Post‐transplant lymphoproliferative disease of donor origin, following haematopoietic stem cell transplantation in a patient with blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare condition that originates from dendritic cells. We report on the first case of Epstein–Barr virus (EBV)‐driven post‐transplant lymphoproliferative disorder (PTLD) of donor origin in a BPDC patient post‐allogeneic haematopoietic stem cell transplantation (HSCT). Flow cytometry study identified a cell population CD4+/CD56+/CD45RA+/CD123+/TCL1+ suggestive of BPDCN diagnosis, which was confirmed by a lymph node biopsy (cells positive for BCL11a, BDCA‐2, CD2AP, CD123, TCL1 and S100). Cytogenetic analysis revealed a complex karyotype: (19 metaphase) 47,XX,t(1;6)(q21;q2?5),‐13 + 2mar[11]/47, XX, +21 [3]/46,XX [5]. The patient was started on acute myeloid leukaemia (AML) induction schedule, and subsequently an allogeneic HSCT was performed. On day +36 post‐HSCT, bone marrow biopsy/aspirate showed complete morphological remission, and chimerism study showed 100% donor chimera. However, on day +37, the patient was found to have enlarged cervical and supraclavicular lymphoadenopathy, splenomegaly and raised lactic dehydrogenase. EBV‐DNA copies in blood were elevated, consistent with a lytic cycle. A lymph node biopsy showed EBV encoded RNA and large atypical B cells (CD45dim−, CD4+/CD56+, monoclonal for k‐chain, CD19+/CD20+/CD21+/CD22+/CD38+/CD43+/CD79β−/CD5−/CD10−), consistent with PTLD monomorphic type. Chimerism study showed that PTLD was of donor origin. This case together with the recent literature findings on BPDCN and PTLD are discussed. Copyright

Favourable/Intermediate ELN-Risk Acute Myeloid Leukemia to Transplant or Not to Transplant First-Line?

Favourable/intermediate ELN-risk acute myeloid leukemias (AMLs) (e.g. those harboring t(8;21) or inv(16) or NPM1A mutations or CEBP-alpha bi-allelic mutations) account for 30% to 50% of all newly diagnosed AMLs [1,2]. In this setting, conventional induction treatments may induce complete remission (CR) in up to 70% to 80%, but relapses still occur in 40% to 50% of cases and, at the end, no more than 30% to 40% of patients can be cured. Therefore, the optimization of post- remission therapy represents the greatest challenge in the treatment of favourable/intermediate-I ELN-risk AML.

Clinical Care of Hematological Patients in a Bone Marrow Transplant Unit: Do Human Resources Influence Infection Incidence?

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