Prognostic value of [<Superscript>18</Superscript>F]FDG-PET/CT in multiple myeloma patients before and after allogeneic hematopoietic cell transplantation

Purpose

Despite improved treatment options, multiple myeloma (MM) remains an incurable disease. The aim of this study was to investigate the prognostic value of positron emission tomography/computed tomography (PET/CT) using ¹⁸F-2’-deoxy-2’-fluorodeoxyglucose ([¹⁸F]FDG) in MM patients shortly before and ~100 days after allogeneic hematopoietic cell transplantation (allo-HCT).

Methods

In this retrospective analysis, we evaluated [¹⁸F]FDG-PET/CT-scans of 45 heavily pre-treated MM patients before and 27 patients after scheduled allo-HCT. All scans were qualitatively and semi-quantitatively assessed for the presence of active disease. Serological response was recorded according to International Myeloma Working Group (IMWG) criteria. Progression-free (PFS) and overall survival (OS) were correlated with different PET/CT-derived parameters, such as presence, number and maximum standardized uptake value (SUV_max) of focal myeloma lesions. The impact of extramedullary disease on patient outcome was also assessed.

Results

PET/CT negativity -prior to or following allo-HCT- was a favorable prognostic factor for progression-free and overall survival (both, PFS and OS: pre-HSCT p?<?0.001, post-HCT p?<?0.005). High FDG-uptake (SUV_max?>?6.5) revealed a significantly shortened survival compared to patients with a lower SUV_max (<6.5) (OS, 5.0?±?1.1 m vs. not reached - longest 122.0 m; p?<?0.001). Moreover, our data prove that a higher number (>3) of focal lesions (pre-HCT: both PFS and OS: p?<?0.001; post-HCT PFS: p?<?0.001, OS: p?=?0.139) as well as the presence of extramedullary disease serve as adverse prognostic factors prior to and after allo-HCT. At response assessment after allo-HCT, [¹⁸F]FDG-PET/CT had a complementary value in prognostication in addition to IMWG criteria alone.

Conclusion

[¹⁸F]FDG-PET/CT before and shortly after allogeneic HCT is a powerful predictor for progression-free and overall survival in MM patients.

     

Ischemic necrosis of the entire femoral head and rapidly destructive hip disease: potential causative relationship

 Objective. Rapidly destructive hip disease (RDHD) is an uncommon disorder of the hip that has been considered a disease of unknown cause and distinct from ischemic necrosis of the femoral head. The objective of this study was to investigate ischemic necrosis of the femoral head as one potential cause of RDHD. Design and patients. In 600 patients who underwent MR imaging of the hip, 20 cases of ischemic necrosis involving the entire femoral head in 18 patients (3%) were retrospectively studied with routine radiography and MR imaging. All patients had surgically confirmed ischemic necrosis of the femoral head. Results and conclusions. All patients showed rapid destruction of the femoral head on routine radiography and MR imaging as compared with the gradual onset of clinical symptoms. Plain radiographs showed several bone fragments at the inferomedial aspect of the femoral head (75%), acetabular erosions (55%), eccentric depression at the lateral articular surface of the femoral head conforming to the adjacent acetabulum (35%), and mild osteoarthritis (15%). Bone sclerosis was often present at sites of impaction between the femoral head and the acetabulum. MR imaging showed marked distention of the joint capsule in all cases. In 14 of 20 cases, the contents of the joint space showed predominantly low or intermediate signal intensity on T1- and T2-weighted images. Ischemic necrosis involving the entire femoral head may represent one of the causes of RDHD.     

Rapidly enhancing hepatic hemangiomas at MRI: Distinction from malignancies with T2-weighted images

The purpose of this study is to describe a subset of atypical hepatic hemangiomas that enhance rapidly and diffusely and to determine whether heavily T2-weighted images could distinguish between atypically enhancing liver hemangiomas and hypervascular malignancies. A retrospective search of MR records identified seven patients with liver hemangiomas that demonstrated diffuse early enhancement and 23 patients with biopsy-proven malignant liver lesions that were hypervascular on dynamic gadolinium-enhanced MR images. Quantitative analysis of signal intensity measurements was performed on the T2-weighted images, heavily T2-weighted (TE < 140), and dynamic gadolinium-enhanced images. Blinded reader comparison of the T2-weighted images and gadolinium-enhanced images was performed. Hypervascular hemangiomas enhanced to a greater degree than hypervascular malignant liver lesions on the early phase gadolinium-enhanced images. Perilesional parenchymal enhancement was demonstrated in five cases of rapidly enhancing hemangiomas. Signal intensity and contrast-to-noise ratios on the heavily T2-weighted images of the hemangiomas were significantly greater than that of the hypervascular malignant lesions (P < .05). Hemangiomas were differentiated from the hypervascular malignant liver lesions with high accuracy (97–100%) by three blinded readers based on the T2-weighted images. A subset of hemangiomas have atypical rapid diffuse enhancement on dynamic gadolinium-enhanced images. These atypical hemangiomas can be distinguished from hypervascular malignant liver lesions on T2-weighted MR images.     

Changes in serum proteins and protein-bound carbohydrates in diabetes mellitus

Summary Studies of serum proteins and protein-bound carbohydrates were carried out on twenty-one diabetics without proteinuria and twenty controls. The diabetics had depression of serum total protein and albumin levels, and elevation of levels of all four types of protein-bound carbohydrate. The degree of elevation was greatest for fucose and least for sialic acid. When the diabetic group was divided into patients with and without evidence of retinopathy or neuropathy, the only significant difference found was an increase of alpha 2-globulin in diabetics with these sequelae. Alpha 2-globulin levels were found to be correlated with both fasting plasma glucose and duration of diabetes. Alpha 2-macroglobulin levels were elevated equally in diabetics with and without sequelae, and appeared related to atherosclerosis rather than to diabetes mellitus. Although disorders other than diabetes increase the magnitude of protein-bound carbohydrate elevation seen, their presence or absence has little influence on the fucose-dominated pattern of elevation found.Some of the material reported here was initially published in abstract form in Clinical Research 16, 129, 1968.     

New Lymphocyte Antigen System (Lna) Controlled by the Ir Region of the Mouse H-2 Complex

A new system of lymphocyte alloantigens in mice is described. This Lna (lymph-node antigen) system is associated with the Ir region of the H-2 (histocompatibility-2) gene complex. It has the following distinctive characteristics: (1) The gene or genes controlling these antigens has been mapped in the Ir (immune response) region between H-2K and Ss-Slp. (2) The antigens are most readily detectable on lymph-node cells, although they are also expressed on peripheral blood lymphocytes, splenic lymphocytes, and thymocytes. (3) Cytotoxicity against only about half of lymph-node cells is consistently observed. (4) Cytotoxic antibody titers against these antigens are strikingly high-more than 2000 by (51)Cr-release and up to 100,000 in the microcytotoxic test. (5) At least two, probably allelic, forms of the antigen(s) have been defined, one associated with the H-2(k) haplotype and one with the H-2(a) haplotype. (6) Antisera against Lna contain multiple antibody specificities that can be fractionated by absorption either with certain recombinants or with other H-2 halotypes that have crossreactive antigens. The antisera against Lna may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.     

Quantitative radionuclide angiocardiography: Detection and quantitation of left to right shunts

In 105 patients detection and quantitation of left to right shunts was performed using quantitative radionuclide angiocardiography. The radionuclide angiocardiograms were acquired and analyzed by a gamma camera interfaced to a digital computer system. Pulmonary to systemic flow ($\text{Qp}\text{Qs}$) ratios were calculated by analysis of pulmonary time-activity histograms using a gamma variate model. All patients were studied with cardiac catheterization, left ventricular angiocardiography and radionuclide angiocardiography. The radionuclide method allowed precise detection and quantitation of left to right shunts with a $\text{Qp}\text{Qs}$ ratio of 1.2 to 3.0. There was good agreement between the $\text{Qp}\text{Qs}$ ratio calculated by oximetry at cardiac catheterization and radionuclide angiocardiography (r = 0.94). The information gathered with this nontraumatic method appears sufficiently reliable to be used in the management of patients.     

Factors influencing systemic arterial oxygen saturation in complete transposition of the great arteries

Hemodynamic data from 100 patients with complete transposition of the great arteries, all 1 year old or older, were reviewed. Only 2 patients, at rest and breathing room air, had a systemic arterial oxygen saturation level as high as 85 percent. In any patient with dextrotransposition of the great arteries and a systemic arterial saturation of 85 percent or greater, there is a strong likelihood of a single ventricle.

At a given level of oxygen consumption, 3 potential variables influence systemic arterial oxygen saturation in transposition: (1) magnitude of the intercirculatory mixing, (2) hemoglobin concentration and (3) magnitude of the recirculated systemic mixed venous flow. The first 2 factors are directly related to systemic saturation, and the third is inversely related.

Decreasing total pulmonary blood flow, secondary to increasing pulmonary vascular disease or pulmonary stenosis, results in decreased intercirculatory mixing and a decrease in systemic arterial oxygen saturation. This decrease in saturation is partially compensated for by an increase in hemoglobin concentration. An index calculated from the level of systemic arterial oxygen saturation divided by the value for hemoglobin concentration is useful in follow-up studies to determine the presence of pulmonary vascular disease or pulmonary stenosis. This index will often eliminate the need for repeated cardiac catheterizations before definitive corrective surgery is carried out.