Bone Marrow Histology in Hemophagocytic Lymphohistiocytosis.

CONTEXT.­: Bone marrow (BM) samples are obtained through aspiration and trephine biopsy. Hemophagocytic lymphohistiocytosis (HLH) has been largely studied in BM aspirate smears. OBJECTIVE.­: To investigate the histologic features of HLH in trephine biopsy. DESIGN.­: Patients with hemophagocytosis in BM aspirate smears were assigned to HLH (n = 127) and non-HLH (n = 203) groups. We quantified hematoxylin-eosin and CD68 immunohistochemical staining of their trephine biopsies. RESULTS.­: No significant correlation was noted in the hemophagocytosis count between aspirate smears and trephine biopsies. Compared with the non-HLH group, the HLH group had a higher hemophagocytosis count (13 versus 9 per tissue section, P = .046), lower percentage of the adipocytic area (36.7% versus 50.3%, P < .001), and higher percentage of the foamy area (19.1% versus 14.5%, P < .001). The HLH group had more histiocyte infiltrates (total histiocyte density, 9.2% versus 7.3%; P < .001) and more fat-infiltrating histiocytes (histiocyte density of the fat-associated part [HD-FA], 7.6% versus 6.2%; P < .001). We identified the following poor prognostic factors in the HLH group: age 50 years or older (median overall survival [mOS], 95 versus 499 days; P = .04), Epstein-Barr virus-positive T-cell lymphoproliferative diseases (EBV+TLPDs) (mOS, 51 versus 425 days; P < .001), hemophagocytosis count of 6 or higher per tissue section (mOS, 66 versus 435 days; P = .02), and HD-FA of 9% or greater (mOS, 61 versus 359 days; P = .02). Multivariate analysis revealed that age 50 years or older (hazard ratio [HR], 2.38; P < .001), EBV+TLPDs (HR, 2.07; P < .001), and hemophagocytosis count of 6 or higher per tissue section (HR, 2.07; P = .002) were independent prognostic factors for HLH. CONCLUSIONS.­: The HLH group had higher hemophagocytic activity, higher cellularity, a more foamy appearance, more histiocyte infiltrates, and more fat-infiltrating histiocytes. High hemophagocytic activity and marked histiocyte infiltrates in the BM fat were associated with poorer prognosis.

Lineage switch of KMT2A-rearranged adult B-lineage acute lymphoblastic leukemia following bispecific T-cell engager and monoclonal antibody therapy.

Adult B-lineage acute lymphoblastic leukemia (B-ALL) with t(4;11)(q21;q23) is very rare. It is characterized by mixed-lineage leukemia and has the potential for lineage switching during the treatment course. We report the disease course of a patient with B-ALL with t(4;11)(q21;q23) to demonstrate that close monitoring of cell morphology and immunophenotyping is necessary to capture the lineage switch at an early stage. Cell morphology, immunophenotyping, and cytogenetics were used to evaluate the patient's disease status. A 36-year-old woman was diagnosed with B-ALL with t(4;11)(q21;q23), which encodes the KMT2A::AFF1 fusion. After the initial induction chemotherapy, her disease remained refractory, and the patient received salvage immunotherapy with blinatumomab and inotuzumab ozogamicin. However, the ALL did not respond. Repeated bone marrow examinations unexpectedly revealed the emergence of a major population of monoblasts, in addition to a minor population of the original B lymphoblasts. The patient was diagnosed with disease evolution from B-ALL to mixed-phenotype acute leukemia (MPAL, B/myeloid). We present this case to highlight the potential of KMT2A-rearranged B-ALL to undergo lineage switch following B-cell targeted therapy. Patients with this kind of B-ALL should therefore be closely monitored to capture potential changes in the nature of the disease and prompt appropriate treatment.

Practically acquired and modified cone-beam computed tomography images for accurate dose calculation in head and neck cancer.

BACKGROUND: On-line cone-beam computed tomography (CBCT) may be used to reconstruct the dose for geometric changes of patients and tumors during radiotherapy course. This study is to establish a practical method to modify the CBCT for accurate dose calculation in head and neck cancer. PATIENTS AND METHODS: Fan-beam CT (FBCT) and Elekta's CBCT were used to acquire images. The CT numbers for different materials on CBCT were mathematically modified to match them with FBCT. Three phantoms were scanned by FBCT and CBCT for image uniformity, spatial resolution, and CT numbers, and to compare the dose distribution from orthogonal beams. A Rando phantom was scanned and planned with intensity-modulated radiation therapy (IMRT). Finally, two nasopharyngeal cancer patients treated with IMRT had their CBCT image sets calculated for dose comparison. RESULTS: With 360° acquisition of CBCT and high-resolution reconstruction, the uniformity of CT number distribution was improved and the otherwise large variations for background and high-density materials were reduced significantly. The dose difference between FBCT and CBCT was < 2% in phantoms. In the Rando phantom and the patients, the dose-volume histograms were similar. The corresponding isodose curves covering ≥ 90% of prescribed dose on FBCT and CBCT were close to each other (within 2 mm). Most dosimetric differences were from the setup errors related to the interval changes in body shape and tumor response. CONCLUSION: The specific CBCT acquisition, reconstruction, and CT number modification can generate accurate dose calculation for the potential use in adaptive radiotherapy.

Treatment and dosimetric advantages between VMAT, IMRT, and helical tomotherapy in prostate cancer.

We investigated the possible treatment and dosimetric advantage of volumetric modulated arc therapy (VMAT) over step-and-shoot intensity-modulated radiation therapy (step-and-hhoot IMRT) and helical tomotherapy (HT). Twelve prostate cancer patients undergoing VMAT to the prostate were included. Three treatment plans (VMAT, step-and-shoot IMRT, HT) were generated for each patient. The doses to clinical target volume and 95% of planning target volume were both ≥ 78 Gy. Target coverage, conformity index, dose to rectum/bladder, monitor units (MU), treatment time, equivalent uniform dose (EUD), normal tissue complication probability (NTCP) of targets, and rectum/bladder were compared between techniques. HT provided superior conformity and significantly less rectal volume exposed to 65 Gy and 40 Gy, as well as EUD/NTCP of rectum than step-and-shoot IMRT, whereas VMAT had a slight dosimetric advantage over step-and-shoot IMRT. Notably, significantly lower MUs were needed for VMAT (309.7 ± 35.4) and step-and-shoot IMRT (336.1 ± 16.8) than for HT (3368 ± 638.7) (p < 0.001). The treatment time (minutes) was significantly shorter for VMAT (2.6 ± 0.5) than step-and-shoot IMRT (3.8 ± 0.3) and HT (3.8 ± 0.6) (p < 0.001). Dose verification of VMAT using point dose and film dosimetry met the accepted criteria. VMAT and step-and-shoot IMRT have comparable dosimetry, but treatment efficiency is significantly higher for VMAT than for step-and-shoot IMRT and HT.