Recombinant human FGF18 preserves depth-dependent mechanical inhomogeneity in articular cartilage.

Articular cartilage is a specialised tissue that has a relatively homogenous endogenous cell population but a diverse extracellular matrix (ECM), with depth-dependent mechanical properties. Repair of this tissue remains an elusive clinical goal, with biological interventions preferred to arthroplasty in younger patients. Osteochondral transplantation (OCT) has emerged for the treatment of cartilage defects and osteoarthritis. Fresh allografts stored at 4 °C have been utilised, though matrix and cell viability loss remains an issue. To address this, several studies have developed media formulations to maintain cartilage explants in vitro. One promising factor for these applications is sprifermin, a human-recombinant fibroblast growth factor-18, which stimulates chondrocyte proliferation and matrix synthesis and is in clinical trials for the treatment of osteoarthritis. The study hypothesis was that addition of sprifermin during storage would maintain the unique depth-dependent mechanical profile of articular cartilage explants, a feature not often evaluated. Explants were maintained for up to 6 weeks with or without a weekly 24 h exposure to sprifermin (100 ng/mL) and the compressive modulus was assessed. Results showed that sprifermin-treated samples maintained their depth-dependent mechanical profile through 3 weeks, whereas untreated samples lost their mechanical integrity over 1 week of culture. Sprifermin also affected ECM balance by maintaining the levels of extracellular collagen and suppressing matrix metalloproteinase production. These findings support the use of sprifermin as a medium additive for OCT allografts during in vitro storage and present a potential mechanism where sprifermin may impact a functional characteristic of articular cartilage in repair strategies.

InP monolithically integrated coherent transmitter.

A novel InP monolithically integrated coherent transmitter has been designed, fabricated and tested. The photonic integrated circuit consists of a distributed Bragg reflector laser and a modified nested Mach-Zehnder modulator having tunable input power splitters. Back-to-back coherent transmission for PDM-QPSK signals is reported up to 10 Gbaud (40 Gb/s) using the integrated laser and up to 32Gbaud (128 Gb/s) using an external low phase noise laser.

Sub-Nyquist field trial using time frequency packed DP-QPSK super-channel within fixed ITU-T grid.

Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super-channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR = 15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SE∙d product of 9254 bit/s/Hz·km was achieved.

Hysterosalpingography in infertility investigation protocol: is it still useful?

PURPOSE OF INVESTIGATION: to assess the radiological findings of women undergoing hysterosalpingography (HSG) as initial infertility investigation protocol. MATERIALS AND METHODS: A retrospective study on infertile women who underwent HSG at Institute of Radiology of Sassari University, Italy. RESULTS: The present case series included 2,845 HSG, performed from January 1997 to March 2014. The age of the patients ranged from 20 to 48 years. The negative exams (tubal patency) were 2,039 out of 2,845 (71.67%). CONCLUSION: A technique of diagnostic imaging for the evaluation of infertility should be non-invasive, not expensive, rapid, of simple execution, and also be able to provide information on tubal patency and pelvic diseases. For these reasons, HSG today remains a useful diagnostic investigation tool in the diagnostic work-up of infertile patients.

A high-throughput model of post-traumatic osteoarthritis using engineered cartilage tissue analogs.

OBJECTIVE: A number of in vitro models of post-traumatic osteoarthritis (PTOA) have been developed to study the effect of mechanical overload on the processes that regulate cartilage degeneration. While such frameworks are critical for the identification therapeutic targets, existing technologies are limited in their throughput capacity. Here, we validate a test platform for high-throughput mechanical injury incorporating engineered cartilage. METHOD: We utilized a high-throughput mechanical testing platform to apply injurious compression to engineered cartilage and determined their strain and strain rate dependent responses to injury. Next, we validated this response by applying the same injury conditions to cartilage explants. Finally, we conducted a pilot screen of putative PTOA therapeutic compounds. RESULTS: Engineered cartilage response to injury was strain dependent, with a 2-fold increase in glycosaminoglycan (GAG) loss at 75% compared to 50% strain. Extensive cell death was observed adjacent to fissures, with membrane rupture corroborated by marked increases in lactate dehydrogenase (LDH) release. Testing of established PTOA therapeutics showed that pan-caspase inhibitor [Z-VAD-FMK (ZVF)] was effective at reducing cell death, while the amphiphilic polymer [Poloxamer 188 (P188)] and the free-radical scavenger [N-Acetyl-L-cysteine (NAC)] reduced GAG loss as compared to injury alone. CONCLUSIONS: The injury response in this engineered cartilage model replicated key features of the response of cartilage explants, validating this system for application of physiologically relevant injurious compression. This study establishes a novel tool for the discovery of mechanisms governing cartilage injury, as well as a screening platform for the identification of new molecules for the treatment of PTOA.

Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial).

This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %) receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 × 10 mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m(2)/day.

Immunomodulating treatment with low dose interleukin-4, interleukin-10 and interleukin-11 in psoriasis vulgaris.

Psoriasis is a chronic inflammatory skin disease affecting approximately 2-3 percent of the world population; it is characterised by hyperproliferation and hyperplasia of the superficial layers of the epidermis. Inappropriate signals released by the immune system determine an altered keratinocyte differentiation, resulting in the formation of desquamating, thickened, inflamed and erythematous plaques. The aim of this investigation was to study the pharmacological activity and safety of three low dose cytokines, Guna-Interleukin 4, Guna-Interleukin 10 and Guna-Interleukin 11 at the concentration of 10 fg/ml in patients affected by moderate to slight psoriasis vulgaris. The multicenter, double-blind, randomized, placebo-controlled clinical trial involved 48 patients who were enrolled and followed up according to a 8-month experimental project. All patients received, according to a cross-over model, either the experimental treatment or placebo, alternatively. Globally, in the 41 evaluated patients it was observed a PASI significant reduction (Friedman test: p=0.00960). The DLQI too decreased significantly in all subjects compared to baseline (Friedman test: p=0.00007). The safety of the treatment with three low dose cytokines administered simultaneously was proved; no adverse event was reported during the whole trial.

Management of breast lobular carcinoma in situ: radio-pathological correlation, clinical implications, and follow-up.

PURPOSE OF INVESTIGATION: To show management of patients with breast lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This study is the retrospective review of 65 patients, between 1996 and 2012, with isolated LCIS of the breast, evaluated through clinical examination, ultrasound, and mammography at the first examination and follow-up. RESULTS: In 53 patients (81.54%), clinical examination was negative. In 14/65 (21.54%) cases, ultrasound was positive and led to biopsy. The clusters of tiny calcifications were the predominant mammographic pattern (45 cases, 69.23%). Forty-six patients (70.77%) underwent surgical biopsy after guided stereotactic placement of metallic marker (hook-wire), 12 (18.46%) by stereotactic vacuum biopsy (SVB), 5 (7.69%) by core needle biopsy (CNB) under ultrasound guidance, two (3.08%) patients CNB with clinically palpable nodules. Fourteen (21.54%) women underwent a quadrantectomy or total mastectomy after the first diagnosis; in this latter group follow-up was negative. Among the 51 patients (78.46%) who did not undergo quadrantectomy or total mastectomy, five relapses occurred, respectively, three LCIS and two infiltrating ductal carcinomas (IDC). Follow-up ranged from 12 to 144 months. CONCLUSION: LCIS is a risk factor for invasive carcinoma and should be managed with careful follow-up, but if there is a discrepancy between pathology and imaging, surgical excision is mandatory.

A case series study on complications after breast augmentation with Macrolane™.

BACKGROUND: The use of Macrolane™ seems to have several advantages compared to the other standard methods for breast augmentation: it is faster, less invasive, and requires only local anesthesia. Nevertheless, various complications associated with the use of Macrolane™ have been described, e.g., encapsulated lumps in breast tissue, infection, and parenchymal fibrosis. We report the results of our case series study on the clinical and imaging evaluations of patients who came to our attention after breast augmentation with Macrolane™ injection and evaluate the effect of this treatment on breast cancer screening procedures. METHODS: Between September 2009 and July 2010, seven patients, treated elsewhere with intramammary Macrolane™ injection for cosmetic purposes, presented to our institution complaining of breast pain. In all patients, Macrolane™ had been injected under local anesthesia in the retromammary space through a surgical cannula. RESULTS: On mammography, nodules appeared as gross lobulated radiopacities with polycyclic contours. On breast ultrasound, the nodules showed hypo-anaechogenic cystlike features. In all cases, image analysis by the radiologist was hindered by the presence of the implanted substance, which did not allow the complete inspection of the whole breast tissue. CONCLUSIONS: From our experience, although safe in other areas, injection of Macrolane™ into breast tissue cannot be recommended at this time. Our study, along with other reports, supports the need to start a clinical trial on the use of injectable fillers in the breast to validate their safety and effectiveness. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Immunohistochemical evaluation of a new epithelial antigen, BER-EP4 in ovarian cancer: a propos of 62 cases.

OBJECTIVE: To assess the immunohistochemical expression of BerEP4, a new epithelial antigen in ovarian cancer. METHODS: We studied 62 cases of ovarian cancer in which BerEP4, CEA and CA-125 were investigated by an immunohistochemical method. We evaluated the correlations among immunohistochemical positivity and the grading, histotype and stage of disease. RESULTS: BerEP4 was positive in 45 out of 62 cases (72.58%), CA-125 in 36 out of 62 cases (58.06%) and CEA in ten out of 62 cases (16.13%). BerEP4 was present both in serous and in mucinous tumors (80.96% vs. 80.77%). CA-125 was mainly expressed in serous vs mucinous tumors (66.67% vs. 57.69%). CEA was more prevalent in mucinous vs. serous tumors. Ber-EP4 was mainly expressed in G1 (75%) and G2 (77.27%). CA-125 was more present in G1 and G3 (both 62.50%) than G2 (50%), whereas CEA showed positivity in G1: 12.50%, G2: 22.73% and G3: 12.50%. There were no differences among the three antigens studied with regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive in 45 out of 62 cases (72.58%) of primary epithelial ovarian cancers. The presence of this antigen seemed to be related to the histotype and grading but not to clinical stage.

CT-guided cryoablation of both breast cancer and lymph node axillary metastasis.

Breast conservation is a major goal of cancer treatment. Many different minimally invasive options have been considered such as cryoablation. This technique is the best visualized of all ablation techniques due to the phase change during ice formation. We describe a case of breast cancer with lymph node axillary metastasis treated by CT-guided cryoablation. Cryoablation may have unique benefits for cost-effective outpatient breast cancer therapy using only local anesthesia and/or mild sedation.

E-learning in radiology: Italian multicentre experience.

PURPOSE: The aim of our work was to design, implement and evaluate an e-learning programme in favour of trainee radiologists enrolled at the many specialty schools located throughout Italy, in the spirit of "sharing culture". MATERIALS AND METHODS: Once a common educational programme and time slot had been identified and planned, the programme was delivered via Internet-based video conferencing once a week for 2-h lectures. Each lecture was followed by interaction between the teaching staff and trainees at the individual sites. The universities involved were Trieste, Udine, Verona, Milano Bicocca, Novara, Varese, Genova, Sassari, Rome "Campus", Rome "Cattolica", Chieti, Foggia, Catania, Modena and Firenze. The University of Rome "Cattolica" participated in the project with two locations: Rome "Policlinico Gemelli" and Rome "Cattolica Campus of Campobasso". RESULTS: Eighteen lectures were conducted, for a total of 36 h. "Transient" connection interruption occurred 13 times for a total of 33 min over 2,160 min of lessons. Video quality and, in particular, details of radiological images shown in slides or moving pictures, were rated as very good by 71% of trainees, good by 24% and satisfactory by 4.5%; no one gave a rating of unsatisfactory. CONCLUSIONS: Based on our experience, whereas e-learning in radiology has become established and compulsory, there is the need for legislation that on the one hand protects online teaching activity and on the other allows study and continuing medical education (CME) credits to be recognised.

A study of three polymorphic sites of the ADA gene in children with type 1 diabetes mellitus.

BACKGROUND: Adenosine deaminase is a polymorphic enzyme that has an important role in immune functions and in the regulation of intracellular and extracellular concentrations of adenosine and adenosine receptor activity. AIM: To search for possible association of type 1 diabetes mellitus (DM1) with three loci haplotypes (ADA1, ADA2, ADA6) of the adenosine deaminase gene. PATIENTS: One hundred and eighty-nine consecutive children with DM1 from Sassari, Sardinia, and a control sample of 239 children from the same area were studied. METHODS: ADA loci genotypes were determined by DNA analysis. RESULTS: Compared to controls, diabetic boys show a decrease of the 2(2)/6(1) haplotype while diabetic girls show an increase of the same haplotype. This association was replicated in an independent sample from Continental Italy. CONCLUSIONS: The 2(2)/6(1) haplotype may exert a protective action in males but may increase susceptibility to DM1 in females: OR = 0.398, 95% CI 0.16-0.96 for males, and OR = 2.31, 95% CI 1.32-4.06 for females.

Application of childhood apraxia of speech clinical markers to French-speaking children: A preliminary study.

PURPOSE: Childhood apraxia of speech (CAS) is difficult to diagnose because there is little agreement on objective clinical markers. Since studies of phonological development in French-speaking children are scarce, there are even fewer recognised markers in French as compared to English. This study aims to determine if a set of operationalised, quantitative measures derived from clinical markers of CAS in English corroborate with clinical CAS diagnosis in French-speaking children. This research contributes to improving differential diagnosis of CAS and phonological disorder cross-linguistically. METHOD: We collected data from five children diagnosed with CAS, nine children diagnosed with phonological disorder, and 75 typically-developing children aged 5.10-9.2 years old. All children were assessed on three speech production tasks: picture-naming, non-word repetition, and diadochokinesis. We extracted 20 quantitative measures corresponding to commonly accepted clinical features of CAS. RESULT: Similar to English-speaking children, French-speaking children with CAS exhibited a high number of vowel errors, consonant and cluster errors, consonant epentheses, devoicing errors, slow diadochokinesis rate, more inconsistency and increased errors with longer words. Contrary to studies on English, these children with CAS did not produce intrusive schwas or vowels. CONCLUSION: This multiple-case study highlights the need for cross-linguistic diagnostic criteria for CAS.

Clinical evaluation of sodium hyaluronate in the treatment of patients with sopraspinatus tendinosis under echographic guide: experimental study of periarticular injections.

PURPOSE: The purpose of this study was to examine the effect of periarticular injection of hyaluronate into shoulders with supraspinatus tendinosis under echographic guide. METHODS AND MATERIALS: The subjects were 56 patients with clinical, echographic and magnetic resonance diagnosis of supraspinatus tendinosis. They were divided in two groups by random sampling; 28 patients were assigned in SH group (sodium hyaluronate) and 28 patients in SC group (sodium chloride). The test drug was 20mg sodium hyaluronate (2ml, Hyalgan, Fidia SpA, Abano T., P.M. 500-700.000, 20mg/2ml). RESULTS: Preliminary results showed that sodium hyaluronate presented the highest efficacy in the improvement of clinical symptoms and recovery of functional status in patients with supraspinatus tendinosis in fact the mean V.A.S. score (Visual Analogue Scale) at 1 month after the end of the infiltrative cycle was 8.0 in the SC group vs. 2.8 in SH group and these numerical data were substantially unchanged also after 3 and 4 months. CONCLUSION: Hyaluronate injection under echographic guide should be use not only as a lubricant but also to prevent articular cartilage degeneration and cover and protect the articular cartilage; indeed sodium hyaluronate can decrease inflammatory joint process.

Feto-maternal ACP1 activity ratio and intrauterine survival.

OBJECTIVE: Genetic differences in the activity of phosphotyrosine phosphatases between mother and embryo could result in a differential activation of signals induced by growth factors in the two sides of placenta. Previous observations suggest that this may have important effects on intrauterine development and survival. The aim of the present study is to confirm previous observations and show new data. STUDY DESIGN: We have studied 573 mother/newborn pairs, 169 wife/husband couples with repeated spontaneous abortion and 34 fertile wife/husband couples RESULTS: In mother/newborn pairs, the analysis of joint mother/infant ACP1 distribution has shown a deficit of pairs with the mother having low ACP1 S isoform concentration and the infant having high S isoform concentration, and an excess of pairs with the mother having high S isoform concentration and the infant having low S isoform concentration. In RSA couples there is an excess of couples in which the wife has low S isoform concentration and the husband has high S isoform concentration and a deficit of couples in which the wife has high S isoform concentration and the husband has low S isoform concentration. In fertile couples the pattern is reversed. CONCLUSION: The data suggest that when the mother to fetus S isoform concentration ratio is in favour of the mother, the probability of survival of the fetus is greater than in the opposite situation.

Hematopoietic stem cell transplantation for adults with acute promyelocytic leukemia in the ATRA era: a survey of the European Cooperative Group for Blood and Marrow Transplantation.

We performed a survey of the European Cooperative Group for Blood and Marrow Transplantation to analyze the outcome of 625 acute promyelocytic leukemia (APL) patients transplanted with auto- or allogeneic-hematopoietic stem cell transplantation (autoHSCT, alloHSCT) after 1993, in first (CR1) or in second complete remission (CR2). Leukemia-free survival (LFS) at 5 years in CR1 was 69% for 149 patients autografted and 68% for 144 patients allografted, whereas in CR2, LFS was 51% in 195 autoHSCT and 59% in 137 alloHSCT recipients, respectively. In the group of autoHSCT for CR1 (n=149), higher relapse incidence (RI) was associated with shorter time from diagnosis to transplant (<7.6 months); transplant-related mortality (TRM) was increased in older patients (>47 years), whereas for CR2, longer time from diagnosis to transplant (>18 months) was associated with increased LFS and decreased RI. In the alloHSCT group for CR1 (n=144), age (<33 years) was associated with increased LFS and decreased TRM and for CR2 (n=137), the use of mobilized peripheral blood stem cells was associated with decreased TRM. Female recipient, a female donor to male recipient and transplants performed before 1997 were associated with decreased RI. In conclusion, HSCT still appears to have a role in APL, especially for patients in CR2.

ACP1 and offspring sex ratio in smoking puerperae: a study at population level.

BACKGROUND: Data from previous study by our group suggest that in smoking women sex ratio of offspring is higher in newborns carrying ACP1C allele than in other ACP1 genotypes, suggesting that differences observed among human population concerning the effect of smoking may depend in part on this genetic factor. OBJECTIVES: In order to further explore this issue we have studied another population and have analysed the relationship between sex ratio and ACP1C gene frequency at population level. METHODS: The analysis includes 719 consecutive births from Central Italy considered in a previous paper and 5510 consecutive births from Sardinia. Data from English and Japanese populations have also been considered in the analysis. RESULTS: Among newborns not carrying ACP1C there is a decrease of SR among the offspring of smoking mothers, while among newborns carrying the ACP1C allele there is an increase of SR among the offspring of smoking mothers relative to non-smoking mothers. Considering Sardinian, Italian, English and Japanese population there is a linear positive relationship between C allele frequency and SR in smoking mothers. CONCLUSIONS: The present observation suggests an interaction between smoking and ACP1 regarding their effects on sex ratio, by which the presence of the ACP1C allele appears to counteract the effect of smoking. This suggests that genetic background may modify the effects of toxic environmental factors on gamete production and functionality and/or on intrauterine survival.

Total hip prosthesis complication, periprosthetic infection with external fistulizing due to Enterobacter cloacae complex multiple drugs resistance: A clinical case report.

INTRODUCTION: The Enterobacter cloacae is a microorganism found in the intestinal flora of the majority of animals, including humans. Primary infections caused by E. cloacae are rare in immunocompetent patients, but are very common in hospital settings in newborns and immunocompromised patients, and can be aggravated by the insurgence of antibiotic resistance. The incidence of periprosthetic hip infections is just below 2%. CASE PRESENTATION: A 76year old woman with multiple comorbidities underwent surgical implantation of intermediary total hip prosthesis of the left hip, in a different health facility, in February 2014, after the basicervical fracture of the upper femur extremity due to trauma. After an episode of dislocation of the prosthetic implant, in September 2014, she underwent a surgical operation to implant the acetabular component. A month later not in our facility, following a re-hospitalization for the dislocation of the arthroprosthesis, an infection from E. cloacae complex was discovered. After 2 years of chronic infection she came to our attention; the clinical picture featured coxalgia and secreting fistula in the surgical wound. Following a specific antibiotic therapy, carried out intravenously over the course of a month, we decided to intervene removing the left hip arthroprosthesis and placing an antibiotic spacer following the direction deduced from the antibiogram study of August 2016. CONCLUSION: The patient was hospitalized in our facility and 2 months later she underwent another operation to remove the antibiotic spacer and to place a new total hip arthroprosthesis. Multiple swabs showed the complete healing from the infection, which was confirmed a couple of months later.

Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio.

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.