Adenovirus infection in adult patients undergoing allogeneic hematopoietic stem cell transplant: Incidence, clinical management, and outcome.

BACKGROUND: Adenovirus infection (ADVi) is an emergent complication in adult patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with poor outcome. Available data on risk factors and optimal management of ADVi in adult allo-HSCT recipients are limited, and recommendations on monitoring and pre-emptive therapy are mainly based on pediatric data. METHODS: In this single-center, retrospective study, we reported all cases of positive ADV-DNA from adult patients undergoing allo-HSCT in the period 2014-2019. The study aimed to describe the incidence of ADVi at day +180 post-transplant. Secondly to describe timing, clinical presentation, risk factors, and outcome of ADVi and to analyze the application of a screening strategy in our cohort. RESULTS: In 445 allo-HSCT recipients, the day +180 incidence was: 9% (39/445) for ADVi, 5% (24/445) for ADV viremia (ADVv), and 3% (15/445) for localized ADVi. The median time to ADVi was 65 (IQR 19; 94) days after HSCT. ADVv-related mortality was 13% (3/24), all cases occurring with blood max-ADV-DNA > 10^3 cp/mL. Independent risk factors for ADVi were diagnosis of lymphoproliferative disease (p = .011) and acute graft-versus-host-disease (p = .021). CONCLUSIONS: In our cohort, ADVi and ADVv were more frequent than previously reported. ADVv with max-ADV-DNA > 10^3 cp/mL was associated with ADV-related mortality, thus careful monitoring and early initiation of treatment are advisable.

Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis in HLA-Matched and Haploidentical Donor Transplantation for Patients with Hodgkin Lymphoma: A Comparative Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT.

Total Marrow Irradiation for Second Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Advanced Acute Leukemia.

Second allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for patients with acute leukemia who relapse after a first HSCT. Although myeloablative conditioning (MAC) regimens before the first HSCT are considered superior to reduced- intensity conditioning (RIC) in terms of disease control in acute leukemia patients, the optimal conditioning regimen for the second allogeneic HSCT remains controversial. The most important prognostic factors are the remission disease phase at the time of the second HSCT and an interval >12 months from the first HSCT to the second HSCT. Total marrow irradiation (TMI) is an advanced high-precision radiation treatment that delivers therapeutic doses over extensively selected targets while substantially reducing radiation to vital organs compared to conventional total body irradiation (TBI). Here we report the results of a retrospective analysis of second allogeneic HSCT treated with TMI as an MAC regimen with the intent of limiting toxicity. We investigated the efficacy of high dose per fraction TMI in combination with thiotepa, fludarabine, and melphalan in 13 consecutive patients with acute leukemia who had relapsed after a first allogeneic HSCT treated between March 2018 and November 2021. Donor type was haploidentical in 10 patients, unrelated in 2 patients, and HLA-identical sibling in 1 patient. The conditioning regimen consisted of 8 Gy TMI in 5 patients on days -8 and -7 and 12 Gy TMI in 8 patients on days -9 to -7, plus thiotepa 5 mg/kg on day -6, fludarabine 50 mg/day on days -5 to -3, and melphalan 140 mg/day on day -2. The TMI was delivered at the dosage og 4 GY for 2 consecutive days (total = 8 GY) or for 3 consecutive days (total = 12 GY). The median patient age was 45 years (range, 19 to 70 years); 7 patients were in remission, and 6 had active disease at the time of their second allogeneic HSCT. The median time to a neutrophil count of >.5 × 109/L was 16 days (range, 13 to 22 days), and the median time to a platelet count of >20 × 109/L was 20 days (range, 14 to 34 days). All patients showed complete donor chimerism on day +30 post-transplantation. The cumulative incidence of grade I-II acute graft-versus-host disease (GVHD) was 43%, and that of chronic GVHD was 30%. The median duration of follow-up was 1121 days (range, 200 to 1540 days). Day +30 and +100 transplantation-related mortality (TRM) was 0. The overall cumulative incidence of TRM, relapse rate, and disease free-survival were 27%, 7%, and 67%, respectively. This retrospective study demonstrates the safety and efficacy of a hypofractionated TMI conditioning regimen in patients with acute leukemia undergoing second HSCT with encouraging outcomes in terms of engraftment, early toxicity, GVHD, and relapse.

Haploidentical Versus Matched Unrelated Donor Transplants Using Post-Transplantation Cyclophosphamide for Lymphomas.

When using post-transplantation cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis for lymphoma patients, it is currently unknown whether a matched unrelated donor (MUD) or a haploidentical related donor is preferable if both are available. In this study we wanted to test whether using a haploidentical donor has the same results of a MUD. A total of 2140 adults (34% Center for International Blood and Marrow Transplant Research, 66% European Society for Blood and Marrow Transplantation registry) aged ≥18 years who received their first haploidentical hematopoietic cell transplantation (haplo-HCT) or MUD-HCT (8/8 match at HLA-loci A, B, C, and DRB1) for lymphoma using PTCy-based GVHD prophylaxis from 2010 to 2019 were retrospectively analyzed. The majority of both MUD and haploidentical HCTs received reduced intensity/nonmyeloablative conditioning (74% and 77%, respectively) and used a peripheral blood stem cell graft (91% and 60%, respectively) and a 3-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF in 54% and 90%, respectively). Haploidentical HCT has less favorable results versus MUD cohort in terms of overall mortality (hazard ratio [HR= = 1.69; 95% confidence interval [CI], 1.30-2.27; P < .001), progression-free survival (HR=1.39; 95% CI, 1.10-1.79; P = .008), nonrelapse mortality (HR = 1.93; 95% CI, 1.21-3.07; P = .006), platelet engraftment (HR = 0.69; 95% CI, 0.59-0.80; P < .001), acute grade 2-4 GVHD incidence (HR = 1.65; 95% CI, 1.28-2.14; P < .001), and chronic GVHD (HR = 1.79; 95% CI, 1.30-2.48, P < .001). No significant differences were observed in terms of relapse and neutrophil engraftment. Adjusting for propensity score yielded similar results. Whenever MUD is available in a timely manner, it should be preferred over a haploidentical donor when using PTCy-based GVHD prophylaxis for patients with lymphoma.

Acute graft versus host disease 1976-2020: reduced incidence and predictive factors.

We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years (p < 0.00001). The median day of onset of GvHD in the three periods was day +14, day +16, and day +30, respectively (p < 0.0001). The cumulative incidence (CI) of GvHD grades II-IV in the three periods was 47, 24, and 16%, respectively (p < 0.00001). The CI of GvHD grades III-IV was 13, 5, and 4% (p < 0.001). In multivariate analysis, significant predictive factors for GvHD II-IV, on top of year of transplant, were anti-thymocyte globulin (ATG) (RR 0.67, p > 0.001); post-transplant cyclophosphamide (PTCY) (RR 0.41, p < 0.001), a family mismatched donor (RR 1.31, p = 0.03) a matched unrelated donor (RR 2.1, p < 0.001), an unrelated mismatched donor (RR1.8, p = 0.001), donor age above 40 years (RR 1.27, p < 0.001), hematological malignancy-as compared to aplastic anemia (RR 2.3, p < 0.001). When selecting only GvHD grade II, in a multivariate analysis, there was a significant reduction of transplant-related mortality (TRM) for patients grafted in 2001-2010 (RR 0.62, p < 0.0001) and for patients grafted in 2011-2020 (RR 0.35, p < 0.0001) as compared to grafts before the year 2000. A similar reduction in time was seen for patients with GvHD grades III-IV. The overall TRM in the three periods was 30, 22, and 16% (p < 0.0001) and survival was 47, 51, and 58% (p < 0.0001). Relapse risk was unchanged. In conclusion, we showed improved prevention of acute GvHD with time, together with a significant delay in the onset of the disease. Treatment of GvHD has also improved over time, as suggested by both reduced TRM and improved survival in more recent transplant periods.

Myeloma Spine and Bone Damage Score (MSBDS) on Whole-Body Computed Tomography (WBCT): Multiple Reader Agreement in a Multicenter Reliability Study.

Objective: To assess the reliability of the myeloma spine and bone damage score (MSBDS) across multiple readers with different levels of expertise and from different institutions. Methods: A reliability exercise, including 104 data sets of static images and complete CT examinations of patients affected by multiple myeloma (MM), was performed. A complementary imaging atlas provided detailed examples of the MSBDS scores, including low-risk and high-risk lesions. A total of 15 readers testing the MSBDS were evaluated. ICC estimates and their 95% confidence intervals were calculated based on mean rating (k = 15), absolute agreement, a two-way random-effects model and Cronbach's alpha. Results: Overall, the ICC correlation coefficient was 0.87 (95% confidence interval: 0.79-0.92), and the Cronbach's alpha was 0.93 (95% confidence interval: 0.94-0.97). Global inter- and intra-observer agreement among the 15 readers with scores below or equal to 6 points and scores above 6 points were 0.81 (95% C.I.: 0.72-0.86) and 0.94 (95% C.I.:0.91-0.98), respectively. Conclusion: We present a consensus-based semiquantitative scoring systems for CT in MM with a complementary CT imaging atlas including detailed examples of relevant scoring techniques. We found substantial agreement among readers with different levels of experience, thereby supporting the role of the MSBDS for possible large-scale applications. Significance and Innovations • Based on previous work and definitions of the MSBDS, we present real-life reliability data for quantitative bone damage assessment in multiple myeloma (MM) patients on CT. • In this study, reliability for the MSBDS, which was tested on 15 readers with different levels of expertise and from different institutions, was shown to be moderate to excellent. • The complementary CT imaging atlas is expected to enhance unified interpretations of the MSBDS between different professionals dealing with MM patients in their routine clinical practice.

The day 100 score predicts moderate to severe cGVHD, transplant mortality, and survival after hematopoietic cell transplantation.

The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGVHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified 4 independent predictors of moderate-severe cGVHD: gamma-glutamyl transferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l, and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0 to 1), intermediate (2 to 3), and high (4) score. The cumulative incidence of moderate-severe cGVHD was 12%, 20%, and 52% (P < .0001) in the training cohort, and 13%, 24%, and 33% (P = .002) in the validation cohort, respectively. The 5-year cumulative incidence of transplant-related mortality (TRM) was 5%, 14%, 27% (P < .0001) and 5%, 16%, 31% (P < .0001), respectively. The 5-year survival was 64%, 57%, 54% (P = .009) and 70%, 59%, 42% (P = .0008) in the 2 cohorts, respectively. In conclusion, Day100 score predicts cGVHD, TRM, and survival and, if validated in a separate group of patients, could be considered for trials of preemptive therapy.

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells.

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the "adaptive" NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation.

Radiomics and Artificial Intelligence for Outcome Prediction in Multiple Myeloma Patients Undergoing Autologous Transplantation: A Feasibility Study with CT Data.

Multiple myeloma is a plasma cell dyscrasia characterized by focal and non-focal bone lesions. Radiomic techniques extract morphological information from computerized tomography images and exploit them for stratification and risk prediction purposes. However, few papers so far have applied radiomics to multiple myeloma. A retrospective study approved by the institutional review board: n = 51 transplanted patients and n = 33 (64%) with focal lesion analyzed via an open-source toolbox that extracted 109 radiomics features. We also applied a dedicated tool for computing 24 features describing the whole skeleton asset. The redundancy reduction was realized via correlation and principal component analysis. Fuzzy clustering (FC) and Hough transform filtering (HTF) allowed for patient stratification, with effectiveness assessed by four skill scores. The highest sensitivity and critical success index (CSI) were obtained representing each patient, with 17 focal features selected via correlation with the 24 features describing the overall skeletal asset. These scores were higher than the ones associated with a standard cytogenetic classification. The Mann-Whitney U-test showed that three among the 17 imaging descriptors passed the null hypothesis. This AI-based interpretation of radiomics features stratified relapsed and non-relapsed MM patients, showing some potentiality for the determination of the prognostic image-based biomarkers in disease follow-up.

Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party.

The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.

Quantitative Imaging and Radiomics in Multiple Myeloma: A Potential Opportunity?

Multiple Myeloma (MM) is the second most common type of hematological disease and, although it is rare among patients under 40 years of age, its incidence rises in elderly subjects. MM manifestations are usually identified through hyperCalcemia, Renal failure, Anaemia, and lytic Bone lesions (CRAB). In particular, the extent of the bone disease is negatively related to a decreased quality of life in patients and, in general, bone disease in MM increases both morbidity and mortality. The detection of lytic bone lesions on imaging, especially computerized tomography (CT) and Magnetic Resonance Imaging (MRI), is becoming crucial from the clinical viewpoint to separate asymptomatic from symptomatic MM patients and the detection of focal lytic lesions in these imaging data is becoming relevant even when no clinical symptoms are present. Therefore, radiology is pivotal in the staging and accurate management of patients with MM even in early phases of the disease. In this review, we describe the opportunities offered by quantitative imaging and radiomics in multiple myeloma. At the present time there is still high variability in the choice between various imaging methods to study MM patients and high variability in image interpretation with suboptimal agreement among readers even in tertiary centers. Therefore, the potential of medical imaging for patients affected by MM is still to be completely unveiled. In the coming years, new insights to study MM with medical imaging will derive from artificial intelligence (AI) and radiomics usage in different bone lesions and from the wide implementations of quantitative methods to report CT and MRI. Eventually, medical imaging data can be integrated with the patient's outcomes with the purpose of finding radiological biomarkers for predicting the prognostic flow and therapeutic response of the disease.

Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen.

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.

Amino acid depletion triggered by ʟ-asparaginase sensitizes MM cells to carfilzomib by inducing mitochondria ROS-mediated cell death.

Metabolic reprogramming is emerging as a cancer vulnerability that could be therapeutically exploitable using different approaches, including amino acid depletion for those tumors that rely on exogenous amino acids for their maintenance. ʟ-Asparaginase (ASNase) has contributed to a significant improvement in acute lymphoblastic leukemia outcomes; however, toxicity and resistance limit its clinical use in other tumors. Here, we report that, in multiple myeloma (MM) cells, the DNA methylation status is significantly associated with reduced expression of ASNase-related gene signatures, thus suggesting ASNase sensitivity for this tumor. Therefore, we tested the effects of ASNase purified from Erwinia chrysanthemi (Erw-ASNase), combined with the next-generation proteasome inhibitor (PI) carfilzomib. We observed an impressive synergistic effect on MM cells, whereas normal peripheral blood mononuclear cells were not affected. Importantly, this effect was associated with increased reactive oxygen species (ROS) generation, compounded mitochondrial damage, and Nrf2 upregulation, regardless of the c-Myc oncogenic-specific program. Furthermore, the cotreatment resulted in genomic instability and DNA repair mechanism impairment via increased mitochondrial oxidative stress, which further enhanced its antitumor activity. Interestingly, carfilzomib-resistant cells were found to be highly dependent on amino acid starvation, as reflected by their higher sensitivity to Erw-ASNase treatment compared with isogenic cells. Overall, by affecting several cellular programs, Erw-ASNase makes MM cells more vulnerable to carfilzomib, providing proof of concept for clinical use of this combination as a novel strategy to enhance PI sensitivity in MM patients.

Spectrum of magnetic resonance imaging findings in transplanted multiple myeloma patients with hip/pelvic pain (according to MY-RADS): A single center experience.

PURPOSE: The aim of our study is to evaluate the spectrum of MRI findings in transplanted Multiple Myeloma (MM) patients with hip/pelvic pain and to correlate these findings with standard prognostic clinical outcomes. METHODS: A retrospective interpretation of the MRI findings of 54 MM patients with hip/pelvic pain were done according to MY-RADS guidelines. MRI findings included: type of bone marrow involvement and incidental findings (osteonecrosis and fractures). Inter- and intra-reader agreement were calculated using Cohen's kappa test. Survival and relapse rates, type of transplantation and days of hospitalization were correlated with MRI findings. RESULTS: 1/52 patient presented normal bone marrow pattern, 10/52 focal pattern, 26/52 diffuse pattern and 15/52 mixed. No cases of micronodular was reported. Among the incidental findings, n = 6 osteonecrosis and n = 5 pathological fractures were found, with average length of stay higher. The intra- and inter-reader agreement assessing MY-RADS, were good (k value between 0.61-0.8). Focal pattern was most represented in patients with osteonecrosis and the worst survival rate. Diffuse pattern was most represented in relapses. No statistically significant correlations were found between bone marrow infiltration patterns and the type of transplantation. CONCLUSION: MRI can recognize different infiltration patterns and complications in transplanted MM patients with hip/pelvic pain, correlating with clinical parameters.

Subspecialty Second-Opinion in Multiple Myeloma CT: Emphasis on Clinically Significant Lytic Lesions.

Background and objectives: In order to increase the accuracy of lytic lesion detection in multiple myeloma, a dedicated second-opinion interpretation of medical images performed by subspecialty musculoskeletal radiologists could increase accuracy. Therefore, the purpose of this study is to evaluate the added value (increased accuracy) of subspecialty second-opinion (SSO) consultations for Computed Tomography (CT) examinations in Multiple Myeloma (MM) patients undergoing stem cell transplantation on standard computed tomography with a focus on focal lesion detection. Materials and Methods: Approval from the institutional review board was obtained. This retrospective study included 70 MM consecutive patients (mean age, 62 years ± 11.3 (standard deviation); range, 35-88 years) admitted in the last six years. Pre-transplant total-body CT (reported by general radiologists) was the only inclusion criteria. Each of these CT examinations had a second-opinion interpretation by two experienced subspecialty musculoskeletal (MSK) radiologists (13 years of experience and 6 years of experience, mean: 9.5 years), experts in musculoskeletal radiology and bone image interpretation with a focus on lytic lesions. Results: Per lesion intra- and inter-observer agreement between the two radiologists was calculated with K statistics and the results were good (K = 0.67: Confidence Inteval (CI) 95%: 0.61-0.78). When the initial CT reports were compared with the re-interpretation reports, 46 (65%) of the 70 cases (95% CI: 37-75%) had no discrepancy. There was a discrepancy in detecting a clinically unimportant abnormality in 10/70 (14%) patients (95% CI: 7-25%) unlikely to alter patient care or irrelevant to further clinical management. A discrepancy in interpreting a clinically important abnormality was registered in 14/70 (21%) patients for focal lesions. The mean diameter of focal lesions was: 23 mm (95% CI: 5-57 mm). The mean number of focal lesions per patient was 3.4 (95% CI). Conclusions: subspecialty second-opinion consultations in multiple myeloma CT is more accurate to identify lesions, especially lytic lesions, amenable to influence patients' care.

Development and definition of a simplified scoring system in patients with multiple myeloma undergoing stem cells transplantation on standard computed tomography: myeloma spine and bone damage score (MSBDS).

BACKGROUND: In clinical practice, there is the need to optimize imaging usage in MM patients. Accordingly, the aim of this paper was to develop a simple computed tomography (CT) scoring method for MM, able to shorten and simplify the interpretation time with good intra- and inter-reader reliability. This method, named MSBDS (Myeloma Spine and Bone Damage Score) was developed with the final aim to use standard total-body CT in the routine practice of MM centres as a complement of standard evaluations in patients undergoing stem cells transplantation. METHODS: We used a widely accepted consensus formation method and literature research during three structured face-to-face meetings specifically designed to combine opinions from a group of experts with proven experience in multiple myeloma care and/or musculoskeletal CT to facilitate the consensus on the field of study topics and the contents of the MSBDS score. Seven practical requisites for the MSBDS score were agreed. A total of 70 MM patients (mean age, 60 years ±9.2 [standard deviation]; range, 35-70 years) undergoing total-body CT was included to develop MSBDS scores. Patients data were already stored in the Radiological database for other Research studies IRB approved (054/2019). Readers to test the MSDMS were radiologists and clinicians involved in MM care or expert in bone damage scores with different level of experience in musculoskeletal and total body CT. Readers were blinded to the clinical data of the patients. RESULTS: The MSBDS scores based on the consensus work described above and literature analysis was finalized. MSBDS is based on an additive scale with assessment of a total body CT with the bone window one time and includes indicators of structural bone damage and instability or fracture risk. The total score is given by the sum of item scores for abnormalities detected. Its values range from 0 (minimum) to values > 10 where 10 is represented by high-risk patients. In high-risk patients immediate surgical or radiation oncologist consultation is suggested. CONCLUSIONS: The MSBDS descriptive criteria are easy, highly reproducible and can be considered as a strong base for harmonizing total body CT interpretation in multiple myeloma patients undergoing stem cell transplantation.

Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR.

PURPOSE: To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation. PATIENTS AND METHODS: We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide. RESULTS: Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively). CONCLUSION: When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.