New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.

The natural history of Fanconi anemia remains hard to establish because of its rarity and its heterogeneous clinical presentation; since 1994, the Italian Fanconi Anemia Registry has collected clinical, epidemiological and genetic data of Italian Fanconi Anemia patients. This registry includes 180 patients with a confirmed diagnosis of Fanconi anemia who have either been enrolled prospectively, at diagnosis, or later on. After enrollment, follow-up data were periodically collected to assess the clinical course, possible complications and long-term survival; the median follow up was 15.6 years. The main goal of the study was to describe the natural history of Fanconi anemia, focusing on the following variables: family history, disease presentation, development of hematological manifestations, development of malignancies, occurrence of hematopoietic stem cell transplantation and survival. Typical morphological and/or hematological abnormalities and/or growth retardation were the most common manifestations at diagnosis; the majority of patients (77%) exhibited hematological abnormalities at the initial presentation, and almost all (96%) eventually developed hematological manifestations. More than half of the patients (57%) underwent a bone-marrow transplant. The occurrence of cancer was quite rare at diagnosis, whereas the cumulative incidence of malignancies at 10, 20 and 30 years was 5%, 8% and 22% for hematological cancers and 1%, 15% and 32% for solid tumors. Overall survival at 10, 20 and 30 years were 88%, 56% and 37%, respectively; the main causes of death were cancer, complications of the hematological presentation and complications of transplantation. These data clearly confirm the detrimental outcome of Fanconi anemia, with no major improvement in the past decades.

The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA) Leucemia Acuta Linfoblastica (LAL) 2317 protocol investigated the frontline chemotherapy-blinatumomab combination in adult Philadelphia chromosome/BCR::ABL1 rearrangement–negative (Ph–) CD19+ B-lineage acute lymphoblastic leukemia (B-ALL) to improve minimal residual disease (MRD) response and clinical outcome. Two cycles of IV blinatumomab were administered after chemotherapy cycles 3 and 6. The primary end point was the rate of molecular MRD negativity after blinatumomab 1. One hundred forty-nine patients were enrolled (median age, 41 years [range, 18-65]); 132 entered remission, 122 received blinatumomab, and 109 had a pre– and post–blinatumomab 1 MRD assessment. MRD negativity increased from 72% to 93% (P < .001) after blinatumomab, with 23 of 30 MRD-positive patients (73%) becoming MRD negative, fulfilling the primary end point. At a median follow-up of 38.1 months (range, 0.5-62.8), the median overall survival (OS) and disease-free survival (DFS) were not reached, and the estimated 3-year OS and DFS were 71% and 65%, respectively, with an excellent outlook for the patients aged 18 to 40 years who achieved an early MRD negativity (DFS, 92%). Pre-blinatumomab MRD predicted a worse outcome, especially in genetically high-risk patients. Notably, the 3-year survival of blinatumomab-treated patients was 82%. Survival and relapse rates were 91% and 15% in patients assigned to standard chemotherapy, 59% and 35% in patients assigned to hematopoietic stem cell transplantation, and 69% and 19% in transplant recipients, respectively. Blinatumomab toxicity was manageable, with only 8 permanent discontinuations. This chemotherapy-blinatumomab risk-oriented program yielded remarkable results that need further improvement in higher-risk patients displaying early MRD persistence. Blinatumomab should be considered as a standard component of induction/consolidation for adult Ph– B-ALL. This trial was registered at www.ClinicalTrials.gov as #NCT03367299.

Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT.

To prospectively compare contrast material-enhanced harmonic compound ultrasonography (US), computed tomography (CT), and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting nodular infiltration in the spleen of patients with newly diagnosed Hodgkin lymphoma. After institutional review board approval and informed consent, 100 consecutive patients with Hodgkin lymphoma during pretreatment staging were prospectively investigated for possible spleen involvement by comparing harmonic compound US (integrated with intravenous infusion of microbubbles in 33 patients) with CT and FDG PET. Findings indicative of malignant nodules with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, response to treatment was regarded as evidence of lymphoma. Malignant nodules were detected with CT in 13 patients, with FDG PET in 13 patients, and with contrast-enhanced harmonic compound US in 30 patients. Coincidental findings of malignancy with all three imaging techniques occurred in 13 patients; 17 patients had only US-detectable malignant nodules, which showed disappearance or relevant decrease after chemotherapy. Overall, the spleen had nodular infiltration in 30 patients (13 for imaging finding concordance; 17 for typical contrast-enhanced harmonic compound US findings and chemotherapy-related nodule size modifications). Thus, both CT and FDG PET provided false-negative results in 17 of 30 patients compared with contrast-enhanced harmonic compound US, the results of which translated into disease upstaging in 13 patients. Harmonic compound US with contrast enhancement for the characterization of possible nodules provides a higher sensitivity than does CT or FDG PET in the detection of splenic involvement by Hodgkin lymphoma.