Background
Imatinib mesylate (IM) 400 mg daily still represents the gold standard for chronic phase chronic myelogenous leukemia (CP-CML). Currently, the initiation dose of IM is adapted to the body ...weight only in childhood. There are some concerns regarding the adaptation of IM prescription in overweighted patients that may respond poorly to this tyrosine kinase inhibitor (TKI). However, this has not been extensively studied in the first-line setting. In addition, it is known that IM is able to promote weight gain and further, obesity has been identified as a possible risk factor in several solid cancers and leukemias.
Aims
In a retrospective observational monocentric study, we evaluated the impact of the weight and the body mass index (BMI) measured at diagnosis on CP CML patients outcomes, on IM first-line, in terms of survival, responses and kinetics.
Methods
We retrospectively enrolled in this study, newly diagnosed CP CML patients, treated with IM in first-line between 2000 and 2017. Overall survival (OS), progression-free survival (PFS), failure-free survival (FFS, defined as progression to advanced phases death, loss of CHR, CCyR, or MMR, discontinuation of IM for toxicity, primary cytogenetic resistance) were analysed since IM initiation in intention-to-treat. Responses (hematologic, cytogenetic, molecular) were analysed according to standard methods. Molecular results were standardised according to the ELN/Eutos programs since 2003, and were expressed as BCR-ABL (IS) in %. Clinical data were extracted from medical files, weight and height measured for all patients at diagnosis, and later nearly all patients being weighted at each time point. The BMI was categorized into 4 stages according to the OMS classification: underweight (BMI < 18.5), normal weight (18.5 ≤ BMI ≤ 24.9), overweight (25 ≤ BMI ≤ 29.9), and obesity (BMI ≥ 30). Serum Albumin (g/l) was regularly assessed, and the nutritional risk index (NRI) was also calculated.
Results
We enrolled 107 patients in this study, 62 (58%) males, with a median age at diagnosis of 55.36 (17-83) years. Sokal risk and Hasford scores were low for 32% and 39%, Intermediate for 48% and 52%, and high for 20% and 9% respectively, (2 patients unknown). Eutos score was low for 95% of patients. The median BMI at diagnosis was 24.61 (17-44.3) Kg/m2. The median weight at diagnosis was 69 (48-128) Kg. We analysed the patients in 2 groups: A: low + normal BMI (<24.9) and B: overweighted + obese (>25). The median follow-up was 97.3 (3-17) months. Age at diagnosis, Sex ratio, duration on IM, Sokal, Euro, Eutos risk scores, presence of ACA at diagnosis, menopauses women, IM duration were not different between groups A & B. There was significantly more diabetic patients in group B (3 vs 11, p=0.018). The rates of CCyR at 6 months, MMR at 12 months were not different between the 2 groups (38% in group A vs 48.9% in group B, p=0.388; and 48.94% in group A vs 66.67% in group B, p=0.133). The rate of MR4 (56 44.09-71.91% group A vs 67.7 52.60-80.74% group B, p=0.817), MR4.5 (48 33.95-62.05% group A vs 48.9 34.05-63.73% group B, p=0.97) at 5 years were not significantly different.
Five patients died, all in group B, from a lymphoid blast crisis in 1 patient, secondary tumours in 3 (lung, colon, prostate cancer + cholangiocarcinoma) and terminal renal insufficiency in 1. The OS rate at last follow-up was significantly better in low/normal BMI 100% months (A) versus 84.7 71.5-100 % months (B, p=0.022) (Fig 1A), as well as the PFS 100% months versus 86.5 75.-99.7 % months (p=0.027) (Fig 1B).
The FFS rate was not different (p=0.794). Interestingly, 25 (23.4%) patients fulfilling the STIM criteria for Treatment-Free Remission, were 17 in arm A and 8 in arm B. Of note, the BMI regularly increases over time with an increase of 0.045 0.006-0.084 Kg/m2 per month, and patients may become overweighted over time (42% at diagnosis, 45.8% at latest follow-up).
Conclusion
This retrospective analysis on an homogeneous population demonstrates that being overweighted at diagnosis of CP CML, and undergoing IM treatment first-line, selectively impacts on survival. However, the rates of responses do not seem to be altered, and the majority of such patients died from CML unrelated causes, mostly from other cancers. The mechanisms responsible for that are probably complex, multifactorial, and confounding factors may interfere, and finally remain to be deciphered.
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Labussiere-Wallet:Novartis: Speakers Bureau. Nicolini:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte Biosciences: Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; ARIAD: Honoraria, Speakers Bureau.
We report a case of polyarthritis with axial involvement in a young female patient treated for acute lymphoblastic leukemia. Detection in the hip fluid of Ureaplasma urealyticum by broad-range PCR ...followed by electrospray ionization mass spectrometry allowed the diagnosis of septic arthritis and ad integrum recovery upon adapted antibiotic therapy.
The treatment of very elderly patients (≥70 years) with acute myeloid leukemia remains controversial. We present here 302 patients seen over a 14-year period in order to understand the real-world ...treatment patterns and outcomes in this patient population. Less than 25% of patients achieved a complete remission. The median overall survival was 12.4, 11.5 and 2.6 months, with a 3-year rates of 27%, 17% and 6%, for non-acute promyelocytic leukemia patients receiving intensive chemotherapy, lower-intensity therapy or best supportive care (BSC), respectively. In all ages, results were not significantly different among patients receiving low-intensity therapy and intensive chemotherapy, but significantly worse in those treated with BSC only. Similarly, intensive chemotherapy and low-intensity therapy gave better survival rates than BSC in patients with favorable- or intermediate-risk cytogenetics and in those with unfavorable cytogenetics (p < 0.0001 and p = 0.04, respectively).
Background:
Reduced-intensity conditioning (RIC) regimens have led to a dramatic reduction of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The concept ...of RIC is to deliver adequate immunosuppression with manageable graft-versus-host disease (GVHD) and the eventual development of a potent graft-versus-leukemia effect. Nevertheless, GVHD prophylaxis remains a challenging task after allo-HSCT. While the combination of cyclosporine A (CsA) and a short course of methotrexate (Mtx) after transplantation is considered as the gold standard for GVHD prophylaxis after conventional myeloablative allo-HSCT from HLA-identical siblings, there is no consensus on the optimal preventive GVHD prophylaxis after RIC allo-HSCT. On the other hand, recent and ongoing studies are evaluating a promising GVHD prophylaxis strategy using post-transplantation cyclophosphamide (PTCy). The aim of this study is to evaluate the impact of different GVHD prophylaxis used after RIC allo-HSCT in patients receiving peripheral blood stem cells (PBSC) from unrelated donors for hematological malignancies.
Patients and methods:
We evaluated 127 consecutive patients with hematological malignancies who received RIC allo-HSCT and were followed in our center between January 2008 and January 2016; 74 (58%) were males, median age was 58 years (range: 18-70), 52 (41%) had acute myeloid leukemia, 36 (28%) myelodysplastic syndrome, 12 (10%) myeloproliferative syndrome, 9 (7%) Non-Hodgkin lymphoma, 9 (7%) chronic lymphocytic leukemia, 6 (5%) multiple myeloma and 3 (2%) chronic myeloid leukemia. At transplantation, 65 (51%) patients were in complete response (CR) or chronic phase (CP). RIC regimen consisted on fludarabine, intermediate doses of IV busulfan and anti-thymocyte golbulins (ATG) (Thymoblobulin) in 56 (44%) patients and a sequential FLAMSA regimen in 71 (56%) patients and who also received similar doses of ATG (Thymoglobulin). PBSC donors were 10/10 HLA matched in 81 (64%) patients and 9/10 HLA mismatched in 46 (36%) patients. Patients were divided according to GVHD prophylaxis into 3 groups: group 1 consisted on CsA alone with 23 (18%) patients, group 2 include patients who received either CsA + mycophenolate mofetil (MMF), n= 64 (50%) or CsA + Mtx, n= 20 (16%) or CsA + cyclophosphamide n= 5 (4%), and group 3 included patients receiving CsA + MMF + tacrolimus n= 15 (12%) patients.
Results:
After transplantation, all patients in group 1 engrafted after a median of 17 (3-25) days, 81/89 (91%) engrafted in group 2 after a median of 17 (5-58) days and 14/15 (94%) engrafted in group 3 after a median of 16 (9-24) days. We did not observe any significant impact of the type of GVHD prophylaxis on the 100-day incidence of grade II to IV acute GVHD, which occurred in 6/15 (40%), 34/81 (42%) and 7/14 (50%) for the groups 1, 2 and 3 respectively (p=0.18). Grade III-IV acute GVHD occurred in 3 (20%), 24 (29%) and 5 (33%) in the three groups respectively (p=0.11). Similarly, cumulative incidence of 1 year chronic GVHD was not different between groups 1, 2 and 3 reaching 46%, 43% and 46% respectively (p=0.6) among them 3/15 (20%), 18 (22%) and 3/14 (21%) patients had an extensive form. After a median follow-up of 22 months for surviving patients, although there was no significant difference between the three groups in terms of non-relapse mortality, we observed more infection-related mortality with 45% and 83% in groups 2 and 3 respectively compared to 47% in group 1. The cumulative incidence of relapse at 2 years was 22%, 31 and 26% for the three groups respectively (p=0.23). Overall survival rates at two years were 43%, 31% and 44 % for groups 1, 2 and 3 respectively (p=0.42). The multivariate analysis taking into account the type of disease, donor HLA matching, disease status at transplantation, type of RIC and the type of prophylaxis, showed that the incidence of acute GVHD was influenced only by the use of FLAMSA regimen from mismatched donors, HR= 2.2 1.3-3.1, p=0.05 which had also the same impact on the occurrence of chronic GVHD.
Conclusion:
Despite its limitations and the need for prospective randomized studies, the results of our study suggest that in the RIC allo-HSCT from unrelated donors, the different GVHD prophylaxis associations lead to similar GVHD outcomes. Patients with more immunosuppressive drugs had a higher incidence of infection-related mortality and in which PTCy could be a better option.
Nicolini:BMS: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Background & aims
Tyrosine kinase inhibitors (TKI) still in a majority of cases do not cure chronic phase CML (CP-CML) and leave patients in a minimal residual disease state, requiring the indefinite ...continuation of TKI. However, in some patients, these agents are able to induce prolonged disease undetectability leading to TKI-cessation strategies and successful treatment-free remissions (TFR) in some. Stable (≥2 years) undetectability can be observed after Imatinib (IM), Nilotinib (NIL) and Dasatinib (DAS) and TKI-cessation strategies have been developed in these 3 settings. In most studies, the overall molecular relapse rate defined as a loss of MMR, >0.1% BCR-ABL/ABLIS is ~30-50% requiring the re-initiation of a TKI. The aim of this study is to characterize and compare the molecular relapse profiles in 3 cohorts of patients undergoing IM, NIL or DAS-cessation.
Methods
This is a bicentric observational retrospective analysis on a selected cohort of CP-CML patients fulfilling the following criteria: CP-CML since diagnosis; ≥2 years stable undetectable BCR-ABL (with ≥32,000 ABL copies/sample) evaluated on 4-6 consecutive follow-up samples, on IM, NIL, or DAS; first cessation whatever the reason for TKI prescription was; molecular relapse after TKI cessation defined as MMR loss on 1 occasion. Molecular analyses were performed in 2 reference laboratories belonging to the EUTOS/ELN quality control system. Relevant clinical data were extracted from the 2 databases of these centres, following the rules of our country regulations.
Results
We identified 29 patients relapsing after IM, 15 after NIL and 14 after DAS cessation with a median age at TKI cessation of 57, 63, and 62.5 respectively (p=0.80). Interestingly, the male/female ratios were 1.41, 0.87 and 0.55 (p=0.38). Sokal score were respectively (L/I/H/NA): 10/12/6/2 for IM, 3/6/6/0 for NIL, 5/4/4/1 for DAS groups (overall p=0.78). Pre-TKI IFN-awas administered in 6 patients in the IM, 4 in the NIL and 1 in the DAS groups (p=0.42). ACA were present at diagnosis in 2, 1 and 1 patients respectively. Two patients had NIL and 7 DAS, in first-line. MR4.5 duration was 37 months for IM, 24.5 months for NIL and 33 months for DAS. Overall TKI duration until TKI cessation were 86 months for IM, 85 months for NIL and 70 months for DAS (p=0.28). The median interval between MR4.5 and TKI cessation was shorter for NIL (25 Months) than for DAS (33 months, p=0.041). The kinetics of relapse are shown in Figure 1 where the evolution of the BCR-ABL ratio by TKI has been smoothed with a polynomial regression.
Relapses occurred after a median of 3.94 (0.89-7.2) for IM, 5 (0.69-7.6) for NIL and 4 (2.87-7.52) months for DAS (p=0.86). Kaplan-Meier analysis of the molecular disease-free survival (DFS) according to TKI and since TKI cessation is surprisingly not different (log-rank test p=0.95) between the 3 TKI, suggesting that TKI2 do not slow down the kinetics of relapse. When looking at the KM estimates of molecular DFS since stable MR4.5, it seems longer with DAS than with NIL (long-rank test p=0.018), despite the fact that the duration of MR4.5 before cessation was significantly longer with NIL than with DAS. This might suggest a differential effect of these 2 compounds on the BCR-ABL+ stem cell compartment. TKI were re-initiated after a median of 0.9, 0.8 and 0.75 months after relapse for IM, NIL and DAS. After relapse 6 patients switched from IM to NIL, 1 from NIL to Peg-IFN-a, 4 from NIL to DAS, whereas all DAS restarted the same TKI. MR4.5 was regained after 6.5, 3.9 and 7.41 months in the IM, NIL and DAS groups with a median follow-up of 43, 23.75 and 25 months after relapse respectively. Two patients died, 1 in the IM group from terminal cardiac insufficiency and 1 in the DAS group from metastatic secondary tumor. At last follow-up, patients regained ≥ MMR in all groups except 1 (0.16% at 3 months DAS rechallenge).
Conclusion
Despite its obvious limitations (relatively low number of patients, retrospective non randomized study) this study characterizes the kinetics of molecular relapse after TKI cessation for TFR and might point out differences suggesting that in these patients the BCR-ABL+ cells responsible for relapse might be different, or that the differential kinase inhibition profile by each TKI induces a different behaviour at relapse. However, these data need to be confirmed ideally in a prospective setting.
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Nicolini:Ariad, BMS: Consultancy, Speakers Bureau; Novartis: Speakers Bureau. Dulucq:Novartis: Speakers Bureau. Mahon:Pfizer: Honoraria; Ariad: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria. Etienne:BMS: Speakers Bureau; Pfizer: Speakers Bureau; ARIAD: Speakers Bureau; novartis: Consultancy, Speakers Bureau.
•Active HHV-6 infection occurred in 11.2% of autologous stem cell recipients.•HHV-6 infection is associated with delayed neutrophils and platelets recoveries.•HHV-6 infection is associated to ...increased frequency of non-infectious complications.•Non-infectious complications are more severe when associated to HHV-6 infection.
to prospectively evaluate the incidence and the clinical relevance on hematopoietic reconstitution of HHV-6 infection in autologous hematopoietic stem cell transplantation (ASCT) recipients.
HHV-6 DNA load was measured in whole blood specimens once during the 7 days before stem cell re-infusion and once a week after transplantation until hematopoietic recovery. Active HHV-6 infection was defined by 2 consecutive positive DNA loads.
from July 2012 to February 2015, 196 adult patients undergoing ASCT were enrolled. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19% at 40 days after transplantation. The onset of active HHV-6 infection occurred with a median of 13 days after stem cell re-infusion. HHV-6 infection was associated with an increased frequency of non-infectious complications (OR = 5.05; 95%CI 1.78–14.32; P < 0.001). Moreover, the severity of these non-infectious complications was higher in recipients exhibiting HHV-6 infection (OR = 4.62; 95%CI 1.32–16.2; p < 0.01). Delayed neutrophils 10 (IQR: 8–14) vs 8 (IQR: 6–11) days and platelets recoveries 15 (IQR: 11.8–18.5) vs 8 (IQR: 4–14) days were observed in patients with active HHV-6 infection compared to non-infected ones.
in this study, 11.2% ASCT recipients presented active HHV-6 infection associated with significantly delayed hematologic reconstitution.
Introduction
Up to 10% of patients (pts) with chronic myeloid leukemia (CML) are already in accelerated phase (AP) at diagnosis and despite treatment advances in the field of tyrosine kinase ...inhibitors (TKIs), management of these pts is challenging. This study aims to examine the benefit of second generation BCR-ABL tyrosine kinase inhibitors (TKI2) as first-line treatment for newly diagnosed AP-CML.
Methods
Pts meeting criteria for AP-CML at diagnosis and treated with first-line TKI2 (i. e. Nilotinib or Dasatinib) were included in this retrospective multicenter observational national study. AP-CML were defined according to the ELN (Baccarani, Blood 2013) as hematological acceleration (HEM-AP, any of the following features: blasts in PB or marrow 15-29%, or blasts+promyelocytes in PB or marrow >30% with blasts <30%, basophils in PB ≥20%, or persistent thrombocytopenia <100×109/L (unrelated to therapy) and/or chromosomal abnormalities in addition to the Ph at diagnosis (ACA-AP). Pts initiated nilotinib at 6-800 mg BID or dasatinib at 100-140 mg QD with further dose adaptations according to toxicities or response. Overall survival (OS), progression-free survival (PFS) and failure-free survival FFS= progression to blast crisis, death, loss of any previous response (CHR, CCyR, or MMR) discontinuation of TKI2 for toxicity, were analysed since TKI2 initiation in intention-to-treat.
Results
Sixty-six pts were analysed: 45 males (68%) and 21 females (32%) with a median age at diagnosis of 49 (15-78.5) years. The median follow-up of the cohort was 43.5 (1.7-117) months. We segregated the pts in HEM-AP (n=33) and ACA-AP (n=33) for further analyses. Nine pts with HEM-AP harboured ACA and were analysed in the HEM-AP group. Fusion transcripts were of the Major BCR in 57 pts, 6 pts had atypical BCR-ABL transcripts (2 e19a2, and 1 e1a2 in the HEM-AP group and 2 e19a2 and 1 Ma3 in the ACA-AP group), and 3 transcripts unknown. Not surprisingly, spleen enlargement was significantly greater in the HEM-AP group 10 (5-14.75) vs. 3 (0-10)cm, p=0.014. PB basophils median 10 (6-16) vs. 3 (2-5)%, p <0.001, PB blasts median: 12.05 (7.5-15) vs. 1.5 (0-4)%, p<.001, as well as PB blasts+promyelocytes median 14 (11-20) vs. 4 (1-7)%, p<.001. Hemoglobin levels were significantly lower in the HEM-AP group median 93 (6-113.5) vs 120 (100-134) g/L, p<0.001. Neither WBC counts, platelets counts, nor BCR-ABL/ABL load differed significantly between the 2 groups. In the ACA-AP group, 10 (30%) pts harbored major route ACA and 23 (70%) pts harbored minor route ACA of whom 3 pts with i(17q) and 1 with 7q abnormalities. In the ACA-AP group, Sokal score was low in 42%, intermediate in 32% and high in 26% of pts (2 pts unknown). Dasatinib was initiated in 19/33 pts (57.5%) in the HEM-AP group and in 8/33 pts (24%) in the ACA-AP group.
Treatment responses did not significantly differ between ACA-AP and HEM-AP group, regardless of the TKI2 administered, with 33/33 (100%) vs 31/33 (94%) pts achieving a CHR, 2/33 (6%) pts vs 0/33 (0%) pts achieving a MCyR, 5/33 (15%) pts vs 5/33 (15%) pts achieving CCyR, 9/33 (27%) pts vs 4/33 (12%) pts achieving a MMR respectively. However, 11/33 (33%) HEM-AP vs 22/33 (66%) ACA-AP pts achieved a deep molecular response (p=0.013, Fisher test). Median times to CHR and MMR were not significantly different between ACA-AP group and HEM-AP group with 1.05 vs 1.25 months (p=0.088) for CHR and 6 vs 7 months (p=0.156) for MMR, respectively.
Overall, the estimated 7-yr FFS rate was 56.92% (95%CI: 40-81), 7-yr PFS was 83.42% (95% CI: 69.6-100%) and 7-yr OS was 87.14% (95%CI: 73.5-100%) (Figure 1.) with no significant differences between ACA-AP vs HEM-AP pts 7-yr FFS: 57.7 vs. 62%, p=0.739; 7-yr PFS: 84.7% vs. 84%, p=0.185; 7-yr OS: 88.9% vs 86.6%, p=0.132 respectively.
There was also no difference in FFS, PFS and OS according to the type of TKI2. The only factors influencing negatively OS were the % of BM blasts (HR=1.17, 95%CI: 1.1-1.28, p<0.001) and the % of BM blasts+promyelocytes (HR=1.14, 95%CI: 1.06-1.22, p<0.001). We identified too few significant factors in univariate analysis to perform a multivariate analysis.
Conclusion
The initiation of a TKI2 in newly diagnosed AP-CML pts induces excellent response and survival rates, probably superior to that of Imatinib first-line, and counterbalances the negative impact of this advanced disease, particularly in HEM AP subgroup.
Etienne:Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Patents & Royalties, Speakers Bureau. Berger:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mahon:Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau; BMS: Speakers Bureau. Rea:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Pfizer: Honoraria. Nicolini:BMS: Consultancy, Speakers Bureau; Incyte Biosciences: Consultancy, Speakers Bureau; Sun Pharma Ltd: Consultancy.
•FLAMSA-BU-conditioned allo-HSCT did not abrogate the negative impact of MRD on survival.•Detectable MRD and refractory status were associated with similar outcomes.•ELN risk stratification was not ...predictive of post-transplantation outcome.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after conditioning with a sequential association of fludarabine, amsacrine, and cytosine arabinoside (FLAMSA) followed by a reduced-intensity conditioning regimen has emerged for patients with high-risk acute myeloid leukemia (AML), especially in refractory or relapsing patients. Here we aimed to address retrospectively the impact of pretransplantation minimal residual disease (MRD) by flow cytometry on the outcomes of high-risk AML patients who underwent allo-HSCT after sequential FLAMSA-busulfan (FLAMSA-Bu)-based conditioning regimens. We included 165 high-risk AML patients who underwent transplantation after FLAMSA-BU in this retrospective single-center “real life” study. All patients received in vivo T cell depletion with antithymocyte globulin (5 mg/kg). MRD detection was based on a leukemia-associated immunophenotype using the European LeukemiaNet recommendations, with a threshold of .1%. Univariate and multivariate analyses were performed using R version 4.1.1 (R Foundation for Statistical Computing, Vienna, Austria). With a median follow-up of 4.0 years post-transplantation, the median overall survival (OS) was 54.9 months. Overall, 41 patients (24.8%) relapsed post-transplantation, with a resulting cumulative incidence of relapse (CIR) of 26.7% at 2 years and 34.0% at 5 years. Detectable MRD preceding allo-HSCT and refractory status were associated with worse median OS and CIR rates compared with patients without detectable MRD; however, OS was not significantly different between pre-HSCT MRD-positive and refractory patients (median, .7 year versus 2.0 years; P = .3). Conversely, pre-HSCT MRD negativity was associated with a reduced 2-year CIR. Neither European LeukemiaNet risk stratification nor age had a significant influence on OS. In the multivariate analysis, only pre-HSCT MRD positivity and lower conditioning regimen intensity were significantly associated with a poorer OS. The cumulative incidence of extensive chronic graft-versus-host disease at 2 years was 26.15%. The estimated nonrelapse mortality (NRM) of the entire cohort at 2 years was 23.1%, with age and unrelated donor identified as risk factors for higher NRM. Our data ahow that FLAMSA-Bu conditioning did not reverse the pejorative effect of detectable pre-HSCT MRD, suggesting that such patients should be offered alternative strategies before HSCT to reach deeper remission.
(A) Overall survival (OS) of patients in complete remission (CR) according to pretransplantation minimal residual disease (MRD) status or refractory status at the time of hematopoietic stem cell transplantation (HSCT). No statistically significant difference was found between patients with detectable pretransplantation MRD and refractory patients (median OS, .7 year versus 2.0 years; P = .3). (B) OS according to pre-HSCT MRD status and conditioning regimen intensity and OS according to pre-HSCT MRD and line of treatment at the time of transplantation. Refractory patients were excluded from this analysis. CR/MRD-, patients in CR with negative pre-HSCT MRD; CR/MRD+, patients in CR with positive pre-HSCT MRD; BU4, patients who received the intensified conditioning regimen; BUCY2, patients who received the reduced-intensity conditioning regimen. Display omitted
Immune reconstitution after allogeneic-hematopoietic-stem-cell transplantation (allo-HSCT) is a complex and individual process. In this cross-sectional study, whole-blood (WB) immune functional assay ...(IFA) was used to characterize immune function by assessing immune-related gene/pathway alterations. The usefulness of this tool in the context of infection, 6 months after transplantation, was evaluated. Sixty allo-HSCT recipients at 6 months after transplantation and 10 healthy volunteers (HV) were included. WB was stimulated in standardized TruCulture tubes using lipopolysaccharides and Staphylococcal enterotoxin B. Gene expression was quantified using a custom 144-gene panel using NanoString nCounter technology and analyzed using Ingenuity Pathway Analysis. The relationships between immune function and clinical characteristics, immune cell counts, and post-transplantation infections were assessed. Allo-HSCT recipients were able to activate similar networks of the innate and adaptive immune response compared to HV, with, nevertheless, a lower intensity. A reduced number and a lower expression of genes associated with immunoregulatory and inflammatory processes were observed in allo-HSCT recipients. The use of immunosuppressive treatments was associated with a protracted immune reconstitution revealed by transcriptomic immunoprofiling. No difference in immune cell counts was observed among patients receiving or not receiving immunosuppressive treatments using a large immunophenotyping panel. Moreover, the expression of a set of genes, including CCL3/CCL4, was significantly lower in patients with Herpesviridae reactivation (32%, 19/60), which once again was not identified using classical immune cell counts. Transcriptional IFA revealed the heterogeneity among allo-HSCT recipients with a reduced immune function, a result that could not be captured by circulating immune cell counts. This highlights the potential added value of this tool for the personalized care of immunocompromised patients.
This study aims to evaluate the impact of implementing a specialized clinical pharmacy program in patients with allogeneic hematopoietic stem cell transplant (HSCT) on their adherence to the ...immunosuppression treatment after discharge. A prospective open interventional design using a retrospective control group was used. The intervention was based on pharmaceutical consultations: the first was performed the day before discharge of HSCT unit and the next consultations during day-care follow-up (weeks 2 and 4 after discharge). Proactive medication reconciliation was implemented with a complete list of medications before the discharge prescription. The discharge prescription summarized on a personalized drug schedule was explained to the patient. The importance of optimal adherence and the potential problems related to self-medication were explained to the patient. Immunosuppression drug adherence was assessed by a direct method using serum levels of calcineurin inhibitors. The potential impact on acute GvHD, and infection was investigated. Twenty-six patients were included in the specialized clinical pharmacy program and 35 patients were in the control group. Seventy-nine pharmaceutical consultations were conducted in the intervention group, lasting a mean 25 min and 16 min for the first and following consultations, respectively. Serum levels in the therapeutic target range were higher in the intervention group (61.5% versus 53.0%, p = 0.07), with greater intra-individual variation (p = 0.005). There was no significant intergroup difference in acute GvHD (53.8% versus 50.3%, p = 0.85) or infection (26.9 versus 22.8%, p = 0.72). The implementation of a specialized clinical pharmacy program for patients who have received allogeneic HSCT seems to be beneficial for immunosuppression drug adherence; this now needs to be confirmed in a multicenter study involving a larger number of patients.
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