Hematology, Transfusion and Cell Therapy最新文献

Introduction/Justification

Triple-refractory multiple myeloma (MM) has a poor prognosis. It is a neoplasm with marked genomic heterogeneity, and recently, our group demonstrated marked uptake of 68Ga-PSMA-11 in some patients, suggesting the potential theranostic use of PSMA in selected cases (1). Herein, we report the initial treatment with 177Lu-PSMA in a patient with refractory MM.

Report

A 76-year-old male patient with IgA/Kappa MM refractory to 6 therapeutic lines, including daratumumab, lenalidomide, and bortezomib, underwent PET/CT with 18F-PSMA-1007, showing marked tracer uptake in multiple osteolytic lesions, several with extensive soft tissue components. A PET/CT with 18F-FDG was also performed, revealing similar findings. A first dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T was administered. The procedure was well tolerated, with slight clinical improvement observed in the week following the infusion. Visual analysis of whole-body scans performed at 21h, 30h, and 7 days demonstrated moderate tracer uptake, lower than that observed with 18F-PSMA-1007. There was slight washout between images at 21h and 30h and moderate/significant washout after 7 days. After 4 weeks, PET/CTs with 18F-PSMA and 18F-FDG were repeated, showing similar findings to the initial scans, with a slight reduction in tracer uptake in some lesions. There was also an increase in the volume of some soft tissue lesions, attributed to post-treatment inflammation. The patient received a second dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T after 6 weeks, and whole-body scans were performed at 2h and 24h, also showing visually lower uptake compared to 18F-PSMA-1007. The patient experienced an intercurrent femoral fracture, limiting mobility for clinical evaluation and subsequent procedures, ultimately leading to their passing after a few days.

Conclusion

This preliminary report suggests that treatment of MM with 177Lu-PSMA is feasible and well tolerated after 2 initial doses. The uptake of 177Lu-PSMA-I&T was visually lower than that of 18F-PSMA-1007, which does not seem to be solely explained by the different resolution of images obtained from different tracers and equipment. There was a slight clinical and imaging response after the first dose, out of a total of 6 planned. A fracture complication and the severity of the case prevented imaging evaluation after the 2nd dose and further treatment continuation. PSMA-177Lu therapy in MM treatment appears to be safe with an initial favorable response, albeit slight. Studies with complete treatments (6 cycles) and in clinically less severe patients are needed to assess the effectiveness of the procedure.

Summary

Theranostic Nuclear Medicine is based on the idea of combining the same molecule (or drug) with different radioisotopes, both for diagnosis and treatment, a concept that emerged in the early 1940s with thyroid diseases. It has since expanded to diseases of higher incidence, such as prostate cancer with several imaging methods used to assess the extent of the disease and the corresponding radiopharmaceuticals used for treatment. For example, by detecting osteoblastic metastases by bone scintigraphy, there are corresponding radiopharmaceuticals with therapeutic properties that eliminate pain from bone metastases, reduce pain of these detected metastases and/or determine overall survival gain. The purpose of this review is to discuss the role and great importance of Theranostic Nuclear Medicine in prostate cancer, addressing the main diagnostic imaging studies with their corresponding treatments, in the Theranostic model.

Conclusão

Nuclear Medicine plays an increasingly significant role in the diagnostic and therapeutic approach to urological malignancies. The enormous advances in SPECT/CT and especially PET/CT images now allow an assessment of these tumors in the staging, recurrence, and response to treatment settings. Molecular imaging identifies alterations not identified by anatomical imaging and for this reason, PET/CT images are becoming increasingly indispensable in specific clinical situations and with precise indications according to the type of urological neoplasia. Theranostic Nuclear Medicine is rapidly evolving in prostate cancer and is a well-established and routine treatment option. Additionally, it is a personalized therapy. The concept of using the same molecule for diagnosis and therapy opened the door to guided and effective treatment, increasing patient survival while maintaining an excellent quality of life and without serious side effects, which is a challenge in metastatic cancer treatments.

Introduction/Justification

Static renal scintigraphy using 99mTc-DMSA is an accurate method for diagnosing and monitoring renal scars and allows for semi-quantification of relative tubular function (RTF). However, in cases of hydronephrosis, radiopharmaceutical accumulation in the pyelocaliceal system may interfere with RTF quantification. Although 24-hour images are typically requested to address this issue, they can inconvenience patients and disrupt the nuclear medicine service routine.

Objectives

This study aimed to assess the impact of additional 24-hour imaging on RTF quantification in patients with hydronephrosis compared to standard 3-hour images.

Materials and Methods

A retrospective analysis was conducted on patients who underwent renal scintigraphy with 99mTc-DMSA, focusing on those who received additional 24-hour imaging. Patients were divided into two groups: those aged up to 12 years (Group 1) and those over 12 years old (Group 2). Planar images were acquired 3 hours post-injection of 175 mBq of 99mTc-DMSA for adults and 1.5 MBq/kg for patients weighing up to 40 kg. Additional delayed images were obtained after 24 hours if pyelocaliceal dilation was present. RTF was calculated using both 3-hour and 24-hour images, preferably using semi-automatic regions of interest. The T-Student test was utilized for statistical analysis, considering a difference of ≤ 3% between the two values as not significantly justifying the additional 24-hour image.

Results

A total of 1,205 consecutive 99mTc-DMSA scans from February 2019 to December 2023 were evaluated. Group 1 comprised 662 patients, with 62 undergoing additional 24-hour imaging, while Group 2 consisted of 543 patients, with 43 undergoing 24-hour imaging. The mean value of the difference between the 3h and 24h images is 1.95% ± 1.83% and median 2 (0 - 6) for Group 1, and 2.40% ± 2.08% and median 2 (0 - 8) for Group 2. Statistical analysis demonstrated equivalence between RTF quantifications obtained at 3-hour and 24-hour imaging for Group 1 p < 0.0001, 95% confidence interval (1.45 - 2.42). However, for Group 2, quantifications at 3-hour and 24-hour imaging were not necessarily equivalent p = 0.0714, 95% confidence interval (1.76 - 3.05).

Conclusion

Additional 24-hour imaging with 99mTc-DMSA in patients under 12 years of age with pyelocaliceal dilation does not appear to impact RTF compared to 3-hour images. However, for older patients, 24-hour imaging is necessary for greater accuracy in RTF determination. Further investigations are warranted to better understand factors influencing RTF calculation, guiding the indication for additional 24-hour imaging.

Summary

Radium-223 (Ra-223) has been used to treat metastatic bone disease in prostate cancer, improving overall survival and quality of life. Breast cancer often presents bone metastasis too, but it is often associated with other sites of disease. In such cases, the addition of Ra-223 to the standard of care (SC) may be beneficial. Therefore, our objective is to determine if the use of Radium-223 plus SC is beneficial for metastatic bone breast cancer patients through a systematic review and meta-analysis. A comprehensive search was conducted across MEDLINE, EMBASE, and CENTRAL databases. The search strategy included the following terms: “Breast cancer” AND “Radium-223”. The selection criteria encompassed both single-arm and randomized controlled trials (RCT). MedCalc® Statistical Software was used. Hazard ratios (HR) were preferred. Odds ratios (OR) or Relative risk (RR) were used when HR was not disponible. For single-arm studies, a proportion meta-analysis was performed. Random-effects methods were used. The initial search yielded 349 articles, 28 articles were reviewed with full-text, and 5 were considered eligible (3 RCT and 2 single-arm studies). SC therapy included: capecitabine, paclitaxel, exemestane plus everolimus and hormonal therapy. Overall, the group submitted to Ra-223 showed a trend to have better symptomatic skeletal event-free survival – SSEFS - (HR: 0.855, CI: 0.643-1.138) and pain improvement (OR: 1.308. CI: 0.780-2.196), but without statistical significance. The pooled analysis showed no difference between arms for serious adverse effects (RR: 0.836. CI: 0.331-2.112). The proportion of SAE in patients submitted to Ra-223 plus SC was 20.1% (CI: 3.6-45.3%).

Conclusão

Ra-223 plus SC in bone metastatic breast cancer patients showed a trend to better SSEFS and pain improvement. However, the low number of RCT studies and the high heterogeneity of SC are great limitations. Results from ongoing RCT (everolimus and avelumab) can change this scenario.

The preoperative clinical and laboratory evaluations of the patient is an essential step to ensure the safety and success of any surgical procedure. This assessment aims to identify any underlying medical conditions and risk factors and determine suitability for surgery. With this step, the medical team can adapt the care plan to meet each patient's specific needs, increasing the chances of a successful procedure. Good clinical assessment and comprehensive laboratory testing, when integrated into a Patient Blood Management approach, are invaluable in promoting safety of care, reducing transfusion risks, improving surgical outcomes, and optimizing resource utilization. This approach not only elevates the quality of care, but is also aligned with evidence-based practice and patient-centered principles, making it an essential component of the perioperative process.

Introduction

Hemoglobinopathy Sβ-thalassemia (HbSβ-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSβ-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSβ-thal and estimated its incidence in Minas Gerais, Brazil.

Methods

Laboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA.

Results

Eighty-nine children were included in the study. Fourteen alleles of β-thal mutations were identified. The incidence of HbSβ-thal in the state was 1 per 22,250 newborns. The most common β^S-haplotypes were CAR and Benin. The most frequent β^thal-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. β-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSβ⁰-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSβ⁺-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSβ⁺-mild ones. β^S-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSβ-thal.

Conclusion

The early identification of β-thalassemia alleles may help the clinical management of these children.