Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing CLL. Minimal Residual Disease (MRD) assessment at 12 months post-HSCT is predictive of relapse. This phase 2 study aimed to achieve M12 MRD negativity (MRDneg) using MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed if failure by donor lymphocytes infusions. Patients had high-risk CLL according to 2006 EBMT consensus, in complete or partial response with lymphadenopathy &lt; 5 cm and comorbidity score ≤ 2. Donors were HLA-matched sibling or matched unrelated (10/10). Forty-two enrolled patients with either 17p deletion (front-line, n=11; relapse n=16) or other high-risk relapse (n=15) received reduced intensity-conditioning regimen before HSCT and were submitted to Md-PII. M12-MRDneg status was achieved in 64% versus 14.2% before HSCT. With a median follow-up of 36 months (range, 19-53), 3-year overall survival, non-relapse mortality and cumulative incidence of relapse are 86.9% (95%CI, 70.8-94.4), 9.5% (95%CI, 3.7-23.4) and 29.6% (95%CI, 17.3-47.7). Incidence of 2-year limited and extensive chronic graft versus host disease (cGVHD) is 38% (95%CI, 23-53) and 23% (95%CI, 10-36) including 2 cases post Md-PII. Fifteen patients converted to MRDneg either after CsA withdrawal (n=12) or after cGVHD (n=3). As a time-dependent variable, MRDneg achievement at any time-point correlates with reduced relapse (HR=0.14 [0.04-0.53], p=0.004) and improvement of both progression free (HR=0.18 [0.06-0.6], p&lt;0.005) and overall (HR: 0.18 [0.03-0.98], p=0.047) survival. These data highlight the value of MRD-driven immune-intervention to induce prompt MRD clearance in the therapy of CLL.</jats:p

Standard chemotherapy followed by allogeneic or autologous transplantation: The role of allogeneic transplantation in the AATT study.

7534 Background: Prognosis of relapsed and refractory T-cell lymphoma patients (pts) is devastating. Early results of the AATT study (Autologous or Allogeneic Transplantation in T-cell lymphoma, Schmitz et al. ASCO 2019; NCT00984412) showed that standard chemotherapy followed by allogeneic transplantation (alloSCT) compared to autoSCT did not improve outcome of poor-risk patients. We wanted to investigate the long-term clinical course of AATT patients (pts) focusing on pts receiving alloSCT off study. Methods: AATT was a randomized trial comparing alloSCT with autoSCT in younger pts (18-60 yrs) with newly diagnosed PTCL who achieved stable disease or better after 4 courses of CHOEP and 1 course of DHAP. Pts were to receive BEAM/autoSCT or myeloablative conditioning/alloSCT from matched related or unrelated donors for consolidation. Local investigators gave updated detailed reports on all further therapy until last follow up or death in order to report long-term EFS and OS focusing on patients receiving alloSCT off study and after failing autoSCT. Results: 103 pts (median age 50 years) randomized to autoSCT (n = 54) or alloSCT (n = 49) formed the full analysis set (FAS), 67 pts (65%) actually received autoSCT (n = 41) or alloSCT (n = 26) (per protocol set, PPS). Median observation time for EFS (OS) was 80 (84) months in the FAS and PPS population. At 7 years EFS and OS were 36% [95%CI: 27% - 46%] and 58% [48-68] for all 103 pts; EFS and OS for patients randomized to autoSCT vs. alloSCT were 34% [22-47] vs. 38% [25-52] and 61% [47-74] vs. 55% [41-69]. For patients actually transplanted 7-year-EFS and -OS were 50% [34-66] vs. 61% [42-80] and 72% [58-86] vs. 61% [42-80]. None of these survival rates differed significantly. TRM was 0/41 (0%) after autoSCT and 8/26 (31%) after alloSCT. Relapse rates were 15/36 (42%) vs. 1/21 (5%) for patients auto- or allografted. Overall, 26/ 50 pts received alloSCT off study because of early relapse/ progression before transplantation or after failing autoSCT. 7-year-OS for these pts is 62% (43-80). Ten of 15 pts relapsing after autoSCT received alloSCT as next therapy. Eight of these pts remain alive 39 – 94 mos after transplantation 5-year-OS of 24 pts who did not receive alloSCT was 17% (2-32). Conclusions: Seven-year OS-rates for the FAS- and the PPS cohort are remarkably high (58% and 68%) reflecting the high rate of long-term survivors after alloSCT also in pts with early relapse and after autoSCT. Pts not undergoing alloSCT had a dismal outcome. For T-cell lymphoma pts with early progression/ relapse after first-line therapy or failing autoSCT alloSCT offers cure in a significant portion of pts and should therefore be the preferred option for all transplant-eligible pts. Clinical trial information: NCT00984412. </jats:p

Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine

Abstract Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts &gt; 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P &lt; 10−4) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P &lt; 10−4). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P &lt; 10−4). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.</jats:p

Scedosporiosis/lomentosporiosis observational study (SOS): Clinical significance of <i>Scedosporium</i> species identification

Abstract Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain.</jats:p

Active Surveillance Program to Increase Awareness on Invasive Fungal Diseases: the French RESSIF Network (2012 to 2018)

The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs.</jats:p