Circulating cell-free DNA improves the molecular characterisation of Ph-negative myeloproliferative neoplasms.

Genetic studies in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) are essential to establish the correct diagnosis and to optimise their management. Recently, it has been demonstrated that it is possible to detect molecular alterations analysing cell-free DNA (cfDNA) in plasma samples, which is known as liquid biopsy. We have assessed the molecular profile of a cohort of 107 MPN patients [33 polycythaemia vera (PV), 56 essential thrombocythaemia (ET), 14 primary myelofibrosis (PMF) and 4 unclassifiable MPN] by next-generation sequencing (NGS) using cfDNA and paired granulocyte DNA. A high concentration of cfDNA in plasma was observed in patients with high molecular complexity, in MPL-mutated cases, and in PMF patients. Targeted sequencing of cfDNA showed a comparable mutational profile (100% accuracy) to the one obtained in granulocytic DNA and a strong correlation was observed between the variant allele frequency (VAF) of gene mutations in both DNA sources. The median VAF detected in cfDNA (29·0%; range: 0·95-91·73%) was significantly higher than the VAF detected in granulocytes (median 25·2%; range: 0·10-95·5%), especially for MPL mutations (44·3% vs. 22·5%). In conclusion, our data support the use of cfDNA as a fast, sensitive and accurate strategy for performing molecular characterisation of MPN patients.

Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia.

The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR-mutated. In low risk patients, time from diagnosis to cytoreduction was shorter in CALR-positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR-mutated ET than in the remaining patients (P = 0·003). In CALR-positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR-mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR-mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.

The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study.

OBJECTIVES: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. METHODS: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. RESULTS: With 7.5 years of median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. CONCLUSIONS: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.

Maintenance therapy with ex vivo expanded lymphokine-activated killer cells and rituximab in patients with follicular lymphoma is safe and may delay disease progression.

Anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) have shown promise in follicular lymphoma (FL) as post-induction therapy, by enhancing antibody-dependent cellular cytotoxicity (ADCC). However, cytotoxic cells are reduced after this treatment. We hypothesised that ex vivo expanded lymphokine-activated killer (LAK) cells administered to FL-remission patients are safe and improve anti-CD20 efficacy. This open, prospective, phase II, single-arm study assessed safety and efficacy of ex vivo expanded LAK cells in 20 FL-remission patients following rituximab maintenance. Mononuclear cells were obtained in odd rituximab cycles and stimulated with interleukin 2 (IL-2) for 8 weeks, after which >5 × 108 LAK cells were injected. Patients were followed-up for 5 years. At the end of maintenance, peripheral blood cells phenotype had not changed markedly. Natural killer, LAK and ADCC activities of mononuclear cells increased significantly after recombinant human IL-2 (rhIL-2) stimulation in all cycles. Rituximab significantly enhanced cytotoxic activity. No patients discontinued treatment. There were no treatment-related serious adverse events. Three patients had progressed by the end of follow-up. After a median (interquartile range) follow-up of 59.4 (43.8-70.9) months, 85% of patients remained progression free. No deaths occurred. Quality-of-life improved throughout the study. Post-induction LAK cells with rituximab seem safe in the long term. Larger studies are warranted to confirm efficacy.

Direct and indirect effects of the SARS-CoV-2 pandemic on Gaucher Disease patients in Spain: Time to reconsider home-based therapies?

OBJECTIVE: An analysis of the SARS-CoV-2 pandemic impact in the Spanish Gaucher Disease (GD) community is presented here. PATIENTS & METHODS: The Spanish GD foundation (FEETEF) surveyed 113 GD patients from March 30 to April 27; all patients provided a verbal consent. RESULTS: 110 surveys were analyzed. The median age was 47 years old (y.o.), 31 patients were ≥ 60 y.o.; and 34% of patients reported comorbidities. 46% (51/110) of patients were treated by enzyme replacement therapy (ERT), 48 of them at hospitals; 45.1% (45/110) were on substrate reduction therapy (SRT) and 9% (10/110) receive no therapy. 25% (11/48) of ERT-hospital-based patients reported therapy interruptions, while SRT-patients did not report missing doses. No bone crises were reported. However, 50% (55/110) of patients reported being worried about their predisposition to a severe SARS-COV-2 infection and 29% (16/55) of them took anxiolytics or antidepressants for this. While 6 patients reported to have contact with an infected person, another two confirmed SARS-CoV-2 infections were reported in splenectomyzed patients, one of them (a 79-year-old diabetic) died. CONCLUSIONS: One quarter of the patients treated at hospitals reported dose interruptions. Home-based therapy may need to be considered in order to minimize the impact of the COVID-19 pandemic.

Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution.

Introduction: The present study evaluates CD30 expression by immunohistochemistry (IHQ) in 216 patients with de novo DLBCL.Methods: CD30 expression was assessed retrospectively in all cases by IHQ. More than >0% and >20% of CD30 expression in the malignant cells were used as a cut-off for positivity. Survival was analysed in 176 patients treated with R-CHOP/R-CHOP-like regimens.Results: CD30 expression >0% was found in 66 (31%) patients, and >20% in 41 (19%). Younger patients <60 years (p = 0.03), good performance status (p = 0.04), and non-GCB subtype (p = 0.004) correlated with CD30 expression. No significant differences were found in overall survival and progression-free survival (PFS), although there was a trend towards better PFS in CD30-positive patients (p = 0.07). Among 7 patients with Epstein-Barr virus (EBV)-positive-DLBCL, CD30 was expressed in 71%, and 2-year PFS significantly inferior compared with CD30-positive EBV-negative-DLBCL patients (p = 0.01).Conclusion: CD30 is expressed in 30% of DLBCL patients, in whom targeted therapy with an anti-CD30 monoclonal antibody could be explored. CD30 is expressed more frequently younger patients, with better performance status and in the non-GCB subtype and its expression trends towards a better PFS. No significant differences regarding characteristics at diagnosis or prognosis were found between groups with different cut-off for positivity.

Life expectancy of follicular lymphoma patients in complete response at 30 months is similar to that of the Spanish general population.

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

The utility of magnetic resonance imaging for bone involvement in Gaucher disease. Assessing more than bone crises.

Bone effects are the most frequent cause of disability in Gaucher disease (GD). Magnetic resonance imaging (MRI) has improved the study of bone involvement making it possible to measure the extent of infiltration and to identify localized complications and other lesions. Here we describe the results of our analysis of all bone lesions registered in MRI studies performed in our GD Clinic. A retrospective study was undertaken for all patients with types 1 and 3 GD who underwent MRI evaluation and correlated with clinical, molecular, and other follow-up information obtained from the Spanish GD Registry. 350 MRI studies of 131 GD patients were reviewed (males 53.4%). Mean age: 37.5years (range 13-74yr), 94.6% (124) were GD1 patients. 113/131 (86.3%) of patients presented with at least one bone effect (bone infiltration, bone crisis, avascular necrosis) were 79.4%, while 28.8% showed another bone lesion such as neuronopathic-like arthropathy, hemangioma, other ischemic phenomena, infection-related lesions, secondary neoplasia and tissue infiltration. MRI is a routinely-used tool for the evaluation of GD lesions which improves the assessment of patients before and during therapy, identifies GD complications and finds other concomitant lesions. This work provides a new evaluation of MRI assessment in this complex rare disease.

Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project.

We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.

Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group.

The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.

Immunoparesis in IgM gammopathies as a useful biomarker to predict disease progression.

BACKGROUND: The management of IgM monoclonal gammopathies undetermined significance (IgM-MGUS) and Waldenstrom's macroglobulinemia (WM) may be challenging. Modern immunoassays that quantify specific monoclonal heavy and light chain immunoglobulins are promising for their use in these applications. METHODS: Ninety consecutive patients (39 IgM-MGUS, 32 indolent WM [iWM], and 19 WM) seen between January 2007 and March 2014 were analyzed. Heavy/light chain (HLC) and serum free light chains assays (FLC) were determined at diagnosis to study their utility as biomarkers in IgM monoclonal gammopathies. RESULTS: The HLC involved to uninvolved IgM ratios (iHLC/uHLC) showed a progressive increase when going from IgM-MGUS, to iWM and to WM (p=0.002). Furthermore, an iHLC/uHLC>62 identified a group of iWM patients with a shorter time-to-progression (TTP) (108 vs. 133 months, p=0.033). Separate analysis of the involved and uninvolved components showed that only the suppression of the uninvolvedimmunoglobulin was predictive of shorter TTP (HR=3.04, p=0.03) suggesting that it could be the majorcontributor to the prognostic value of the Hevylite assay. Additionally, a multivariate analysis showed that immunosuppression (either classical immunoparesis or Hevylite immunosuppression) was an independent prognostic factor (p=0.016) reinforcing its relevance in the disease mechanism. Finally, monoclonal sFLC levels were highest in WM patients, with 83% presenting values>60 mg/L. CONCLUSIONS: The results suggest that the levels of immunosuppression and/or the iHLC/uHLC ratio of IgM immunoglobulins measured by Hevylite are associated with greater disease activity which significantly impacts in the outcome of WM patients and may also help in the differentiation of IgMMGUS from iWM.

Long-term complication in follicular lymphoma: assessing the risk of secondary neoplasm in 242 patients treated or not with 90-yttrium-ibritumomab-tiuxetan.

BACKGROUND: Non-Hodgkin lymphoma patients have a 25% increased risk of secondary primary neoplasms (SPNs). Regarding the controversy about the increased risk of SPN in patients exposed to radioimmunotherapy (RIT), we have analyzed this issue in a cohort of follicular lymphoma (FL) patients treated with/without RIT. PATIENTS AND METHODS: A retrospective study including all consecutive FL patients diagnosed since 2001 was performed. Demographic, clinical data including the incidence of any kind of neoplasm (excluding basocellular skin carcinoma) were recorded. RESULTS: A total of 242 patients were registered, male/female: 103/139, mean age: 59.9 yr (15-86), stage IV (57.8%), and Follicular Lymphoma Prognostic Index (FLIPI) low-risk (62.15%) predominance. Ninety-six patients (39.7%) were treated with 90Y-IT. The median follow-up for patients treated or not with 90Y-IT was 61 (8-273) and 38 (1-171) months. With respect to SPN incidence, 38 (15.6%) patients have at least two cancers, in 17 (44.7%), FL was the SPN; for the rest (226), the global incidence of SPNs was 9.3% (21), but there were no differences related to the exposition or not to 90Y-IT (P = 0.26). In seven patients, more than two (2-6) different therapies were registered; four were exposed to fludarabine-based therapy, three to radiotherapy and two to autologous stem-cell transplantation, and in the RIT cohort, two patients developed myelodysplastic syndrome. CONCLUSION: This is one of the largest single institution reports assessing the risk of SPN in FL patients treated (96) or not (146) with 90Y-IT. It seems that 90Y-IT does not increase significantly the risk of SPN but avoiding its use after fludarabine and other intense cytotoxic schemes is recommended.

Long-term efficacy of (90)Y ibritumomab tiuxetan therapy in follicular non-Hodgkin lymphoma and health-related quality of life.

The aim of this study was to analyze the outcomes of 37 follicular lymphoma (FL) patients treated with (90)ytrium ibritumomab tiuxetan (90Y-IT), outside of clinical trial, according to protocol ISCRTN36210045, after ≥5 years follow-up to February 2014. Health-related quality of life (HRQoL) was evaluated with the SF-36, Spanish version, and compared with the general population of Spain. Patients had a mean age of 61.9 (range, 30-85) years and included 18 males. FLIPI, low: 25 (67.6 %), intermedium 9 (24.3 %), and low 3 (8.1 %). Previous therapy schedules >2: 48.6 % The median follow-up was 66 months, mean Time to Relapse (TTR) 71.3 months (58.8-83.8) median not reached. Thirty-four patients achieved complete response (91.8 %), and three no response. Mean overall survival: 82.3 months (71.6-92.9). Four patients presented with concomitant tumors (colon, breast, prostate, lung) after radioimmunotherapy, and three developed second primary neoplasms (esophagus, renal, and myelodysplastic syndrome in a relapsed patient who received fludarabine). Four of 10 deaths were related to lymphoma progression. Hematological toxicities were mild and easily managed. No patients required hospitalization. Negative scores were obtained in the physical and emotional roles items; however, the perception of general health and vitality were better than in the general population, with the best outcomes in non-relapsed patients. Radioimmunotherapy with 90Y-IT was safe and effective as long-term therapy in patients with FL. Early use of radioimmunotherapy could offer good, sustained responses with low toxicity over the long term and acceptable HRQoL.

Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas.

BACKGROUND: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. METHODS: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. RESULTS: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL, p < 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. CONCLUSIONS: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients.

Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study.

We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

Recommendations on the follow-up of patients with Gaucher disease in Spain: Results from a Delphi survey.

Management of Gaucher disease (GD) is challenging due to its wide genotypic and phenotypic variability and changing clinical manifestations due to effective treatment. Sixteen face-to-face meetings with experts were held in order to discuss daily clinical practice and identify controversies regarding the management of GD. With this information, a questionnaire with 93 recommendations for different clinical scenarios was designed, and a Delphi survey among 86 physicians with experience in GD was conducted. Consensus was reached on 73 out of the 93 items. Recommendations on follow-up of adult and pediatric patients were in line with current guidelines, and underscored the importance of a patient-tailored approach. For the follow-up of stable patients receiving long-term treatment, consensus was reached on the importance of multidisciplinary care that involves pediatricians, internal medicine, and primary care, specialized radiologists, orthopedic surgeons, and hematologists when required. Degree of pain, use of painkillers and antidepressants, and quality of life should be evaluated at every follow-up visit or at least once per year. In general, a closer follow-up was recommended for untreated patients or patients who underwent a treatment change (every 3 months during the first year) and during pregnancy. For pregnant patients, hemostasis and risk of hemorrhage should be assessed, but no consensus was reached for initiation of treatment in asymptomatic pregnant patients. Lastly, recommendations on how to adapt GD management during a COVID-19 pandemic were collected. This expert consensus may help decision-making during the management of GD in specific clinical scenarios.

Advantages of digital technology in the assessment of bone marrow involvement in Gaucher's disease.

Gaucher disease (GD) is a genetic lysosomal disorder characterized by high bone marrow (BM) involvement and skeletal complications. The pathophysiology of these complications is not fully elucidated. Magnetic resonance imaging (MRI) is the gold standard to evaluate BM. This study aimed to apply machine-learning techniques in a cohort of Spanish GD patients by a structured bone marrow MRI reporting model at diagnosis and follow-up to predict the evolution of the bone disease. In total, 441 digitalized MRI studies from 131 patients (M: 69, F:62) were reevaluated by a blinded expert radiologist who applied a structured report template. The studies were classified into categories carried out at different stages as follows: A: baseline; B: between 1 and 4 y of follow-up; C: between 5 and 9 y; and D: after 10 years of follow-up. Demographics, genetics, biomarkers, clinical data, and cumulative years of therapy were included in the model. At the baseline study, the mean age was 37.3 years (1-80), and the median Spanish MRI score (S-MRI) was 8.40 (male patients: 9.10 vs. female patients: 7.71) (p < 0.001). BM clearance was faster and deeper in women during follow-up. Genotypes that do not include the c.1226A>G variant have a higher degree of infiltration and complications (p = 0.017). A random forest machine-learning model identified that BM infiltration degree, age at the start of therapy, and femur infiltration were the most important factors to predict the risk and severity of the bone disease. In conclusion, a structured bone marrow MRI reporting in GD is useful to standardize the collected data and facilitate clinical management and academic collaboration. Artificial intelligence methods applied to these studies can help to predict bone disease complications.