Little is known about the prognostic significance of muscle loss for allogeneic hematopoietic stem cell transplantation (allo-HCT). We retrospectively analyzed consecutive patients who received ...allo-HCT from 2013 to 2015. All patients underwent computed tomography (CT) imaging and bioelectrical impedance analysis (BIA) within 30 days before allo-HCT. Skeletal muscle area (cm
2
) at the third lumbar vertebra level on CT imaging and skeletal muscle mass (kg) measured by BIA were normalized by height in meters squared (m
2
) to calculate the skeletal muscle area index (SMI) and skeletal muscle mass index (SMMI). SMI and SMMI were significantly correlated (
r
= 0.744;
P
< 0.001). The cumulative incidence of 1-year non-relapse mortality (NRM) was significantly higher in patients with low SMI than high SMI (17% versus 0%, respectively;
P
= 0.023). Overall survival was shorter in patients with low SMI than high SMI (56% versus 93%, respectively;
P
< 0.001). In univariate analysis, low SMI was associated with increased risk of NRM (HR 7.46; 95% CI 1.05–52.98;
P
= 0.044), and in multivariate analysis it was associated with higher overall mortality (HR 5.35; 95% CI 1.71–16.72;
P
= 0.004). These results suggest that low muscle mass is an independent predictor of mortality after allo-HCT.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We evaluated the impact of
FLT3
-ITD,
NPM1
mutations, and double mutant
CEBPa
(
dmCEBPa
) on overall survival (OS) after relapse in patients with cytogenetically intermediate-risk acute myeloid ...leukemia (AML) who were treated with chemotherapy alone in the first remission (CR1). Patients aged 16–65 years diagnosed with cytogenetically intermediate-risk AML, and who achieved CR1 were included. We retrospectively analyzed
FLT3
-ITD,
NPM1
mutations and
CEBPa
using samples obtained at diagnosis, which therefore did not affect the therapeutic decisions. Among 235 patients who had achieved CR1, 152 relapsed, and 52% of them achieved second CR. The rate of achieving second CR was significantly higher (85%) in those with
dmCEBPa
. Patients with
FLT3
-ITD had significantly worse OS after relapse than those without (19% vs 41%,
p
= 0.002), while OS was comparable between patients with and without
NPM1
mutations (37% vs 34%,
p
= 0.309). Patients with dm
CEBPa
had improved OS than those without (61% vs 32%,
p
= 0.006). By multivariate analysis,
FLT3
-ITD was independently associated with worse OS after relapse hazard ratio (HR) 1.99, 95% CI 1.27–3.12,
p
= 0.003, and
dmCEBPa
with improved OS (HR 0.40, 95% CI 0.17–0.93,
p
= 0.033). Our data show that screening for these mutations at diagnosis is useful for facilitating effective therapeutic decision-making even after relapse.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To elucidate the incidence, causes, and risk factors associated with readmission due to transplant-related complications, we studied 213 consecutive patients who were discharged without progression ...of primary disease after their first allogeneic hematopoietic cell transplantation at our center between 2013 and 2016. The median patient age was 50 years (range, 18-71 years). Eighty-three patients had AML or MDS, 66 had lymphoma, 28 had ALL, 23 had ATL, and 13 had other diseases. The median duration of hospitalization for transplantation was 56 days (range 27-325 days). The cumulative incidences of readmission due to transplant-related complications were 8% at 30 days, 16% at 100 days, and 25% at 1 year after discharge. The most frequent cause of readmission was infection, followed by graft-versus-host disease throughout the first year. In multivariate analysis, steroid use at discharge was the only risk factor associated with readmission within 30 days, and steroid use at discharge, absolute lymphocyte count < 500/µl at discharge, and documented bacterial infection during admission were risk factors associated with readmission within 1 year. Our results indicated that factors during hospitalization or discharge, but not at transplantation, were associated with readmission. Patients with these risk factors should be monitored carefully after discharge.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
B-cell non-Hodgkin lymphoma (NHL) is the most frequent hematologic malignancy. Despite the refinement of chemoimmunotherapy, a substantial number of patients experience chemorefractory disease. ...Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is considered the most promising and effective therapy to overcome chemorefractory B-cell NHL. Based on the promising results obtained from pivotal trials, the US Food and Drug Administration and European Medicines Agency approved anti-CD19 CAR T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma. Nonetheless, there remain several controversial issues and problems awaiting solutions, including optimal management of toxicities, overcoming relapsed/refractory disease after CAR T-cell therapy, and improving CAR-T manufacturing platform. Definite unmet medical needs among patients with chemorefractory B-cell NHL still exist. CAR T-cell therapy might be a game changer that can defeat chemorefractory B-cell NHL, and further clinical development is warranted. In this review, we summarize the recent clinical developments, clinical implications, and perspectives of CAR T-cell therapy, focusing on B-cell NHL.
Purpose
Advances in allogeneic hematopoietic cell transplantation (allo-HCT) have resulted in a growing number of transplant survivors; however, long-term survivors are at risk of developing late ...complications, and published guidelines recommend screening of this population. We conducted a single-center prospective study to evaluate the adherence to and usefulness of recommended screenings at a long-term follow-up (LTFU) clinic.
Methods
We included consecutive patients who received allo-HCT at our center from 2014, as well as post-HCT patients visiting our outpatient clinic. Visits and screenings were planned at 3 months, 6 months, and 1 year after allo-HCT, and annually thereafter. Outcomes were reported by physicians including the incidence of findings at each screening that led to interventions.
Results
Among the 216 participants, 95% visited the LTFU clinic, and 94% completed planned screenings. However, the rate of secondary cancer screenings targeting high-risk subjects was lower (38% to 68%). The overall percentage of screening results leading to interventions was 4.5%, with higher percentages (> 10%) for bone density testing, ophthalmological examinations, dental assessment, upper gastrointestinal endoscopy, and colonoscopy, with two patients diagnosed with secondary cancers.
Conclusions
Although the overall screening rate was high, it should be possible to improve the detection rate of late complications by decreasing screening failures, especially the screening for secondary cancers limited for high-risk survivors. A nationwide effort to educate HCT survivors and health practitioners using standardized nationwide LTFU tools may be effective, along with the development of institutional, local, and nationwide networks to maintain effective follow-up systems.
Mutations of CCAAT/enhancer–binding protein alpha (CEBPAmu) are found in 10% to 15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable ...prognosis; however, single-mutated CEBPA (CEBPAsm) does not seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (P < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged ≤70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .026). Multivariate analysis of 744 patients aged ≤70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio, 0.3287; P < .001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA-mutated AML.
•CEBPA mutation in the bZIP domain is associated with favorable prognosis in de novo AML, even if it was detected as CEBPAsm.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Posttransplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic cell transplantation (HCT) is usually donor derived, associated with Epstein–Barr virus (EBV), and of B-cell origin. ...T-cell PTLD (T-PTLD) after allogeneic HCT is extremely rare. Four of 1015 (0.39%) allogeneic HCT patients were diagnosed with T-PTLD; peripheral T-cell lymphoma-not otherwise specified, anaplastic large cell lymphoma, monomorphic T-cell PTLD and polymorphic PTLD with chronic active EBV infection-like symptoms. Three of the four patients developed T-PTLD within 6 months after HCT from HLA-mismatched unrelated donor. Three (75%) and 4 (100%) cases were positive for EBV-encoded small RNA in situ hybridization and EBV-DNA load in peripheral blood, respectively. Chimerism analysis showed that 75% of T-PTLD tissues (3/4) were recipient derived. T-PTLD was refractory to salvage chemotherapy and fatal in all four patients. Including the 10 patients in the literature, the median interval from HCT to diagnosis of T-PTLD was 5 months (range 1–72 months), 55% were negative for EBV, and 56% were recipient-derived. T-PTLD, which often occurred early after allogeneic HCT, was more likely to be EBV negative and recipient derived than B-cell PTLD after allogeneic HCT. Like T-PTLD after solid organ transplant, T-PTLD after allogeneic HCT demonstrated morphological heterogeneity and poor prognosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The prognostic significance of
FLT3
-tyrosine kinase domain (TKD) mutations remains unknown. To investigate the prognostic impact of
FLT3
-TKD, 676 de novo acute myeloid leukemia (AML), we ...retrospectively analyzed cases and conducted a review of the literature. Of the 676 de novo AML cases, 34 (5.0%) were
FLT3
-TKD-positive; both
FLT3
-TKD and
FLT3
-ITD were noted in only two cases (0.3%). Although no significant differences in relapse-free survival (RFS) were noted,
FLT3
-TKD-positive cases showed better prognoses than
FLT3
-ITD-positive cases (
FLT3
-TKD versus
FLT3
-ITD,
p
= 0.152). For overall survival (OS), although
FLT3
-TKD-positive cases showed prognoses similar to those for
FLT3
-WT cases, their prognoses were significantly better than those of
FLT3
-ITD-positive cases (
FLT3
-TKD versus
FLT3
-ITD,
p
= 0.032). Moreover, the 5-year OS for
FLT3
-TKD-positive cases was 46.1%, indicating that this as an intermediate prognosis group. Although no reports from Asia have indicated a frequency of
FLT3
-TKD-positive cases > 10%, several reports from Europe and the United States have indicated frequencies > 10%. This suggests the possibility that
FLT3
-TKD-positive cases are less common in Asia than in Europe and the United States. We anticipate that in the future, the appearance of targeting agents, such as FLT3 inhibitors, will improve the prognosis of
FLT3
-TKD-positive AML relative to that of
FLT3
-WT AML.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a ...recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy.
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