Diffusion-weighted MRI for staging and evaluation of response in diffuse large B-cell lymphoma: a pilot study.

The aim of this study was to compare diffusion-weighted MRI (DW-MRI) with positron emission tomography/computed tomography (PET/CT) for the staging and evaluation of the treatment response in patients with diffuse large B-cell lymphoma (DLBCL). Institutional review board approval was obtained for this study; all subjects gave informed consent. Twelve patients were imaged before treatment and eight of these were also imaged after two cycles of chemotherapy using both DW-MRI and PET/CT. Up to six target lesions were selected at baseline for response assessment based on International Working Group criteria (nodes > 1.5 cm in diameter; extranodal lesions > 1 cm in diameter). For pretreatment staging, visual analysis of the numbers of nodal and extranodal lesions based on PET/CT was performed. For interim response assessment after cycle 2 of chemotherapy, residual tumor sites were assessed visually and the percentage changes in target lesion size, maximum standardized uptake value (SUVmax ) and apparent diffusion coefficient (ADC) from pretreatment values were calculated. In 12 patients studied pretreatment, there were 46 nodal and 16 extranodal sites of lymphomatous involvement. Agreement between DW-MRI and PET/CT for overall lesion detection was 97% (60/62 tumor sites; 44/46 nodal and 16/16 extranodal lesions) and, for Ann Arbor stage, it was 100%. In the eight patients who had interim assessment, five of their 49 tumor sites remained abnormal on visual analysis of both DW-MRI and PET/CT, and there was one false positive on DW-MRI. Of their 24 target lesions, the mean pretreatment ADC value, tumor size and SUVmax were 772 µm(2) /s, 21.3 cm(2) and 16.9 g/mL, respectively. At interim assessment of the same 24 target lesions, ADC values increased by 85%, tumor size decreased by 74% and SUVmax decreased by 83% (all p < 0.01 versus baseline). DW-MRI provides results comparable with those of PET/CT for staging and early response assessment in patients with DLBCL.

Solitary Intracranial Plasmacytoma of the Brain Treated With Primary Radiation Therapy.

We present a rare case of a solitary intracranial plasmacytoma of the brain parenchyma in a 49-year-old female who presented with neck pain/headache, paresthesias, and auditory hallucinations. A workup revealed a solitary left parietal lobe brain lesion and a biopsy demonstrated a plasma cell infiltrate consistent with an extramedullary plasmacytoma. A complete workup for multiple myeloma was negative. As opposed to surgical resection and adjuvant radiation therapy (RT), as described in prior case reports in the literature, this patient was managed with definitive local RT alone to 50 Gy in 25 fractions. Six months following primary RT completion, the patient's presenting symptoms completely resolved and follow-up imaging revealed regression of the primary tumor. To our knowledge, this is the first reported case of a solitary extramedullary plasmacytoma of the brain treated with localized definitive RT alone.

Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF.

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

Autologous Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients With Multiple Myeloma and Hematopoietic Stem Cell Transplantation.

Multiple myeloma (MM) is the most common indication for autologous hematopoietic stem cell transplantation (HSCT) in North America. Despite occurring in up to 50% of patients undergoing allogeneic HSCT, the incidence of graft-versus-host disease (GVHD) after autologous HSCT is reportedly only 5-20%. Gastrointestinal involvement with graft-versus-host disease (GI GVHD) is a common and serious complication of allogeneic HSCT. GI GVHD after autologous transplant, which is referred to as autologous GVHD (auto-GVHD), has also been described. Auto-GVHD is usually less severe than allogeneic GVHD, and it can be one of the manifestations of engraftment syndrome with release of inflammatory cytokines and infiltration of auto-reactive T cells into affected tissue. Seventy-nine percent of patients respond well to corticosteroids without evidence of recurrence. However, cases of severe auto-GVHD lacking good response to corticosteroids have been reported, most notably in MM patients. Here we present two cases of autologous GI GVHD in recipients of autologous HSCT for treatment of MM. Our cases demonstrate two distinct clinical and endoscopic presentations of this uncommon entity. In the first case, the patient had more severe clinical symptoms accompanied by radiographic, endoscopic, and pathologic findings. The hospital course was complicated by cryptosporidium enteritis and acute cholecystitis in the setting of increased immunosuppression with a corticosteroid for presumed auto-GVHD. In contrast, the second case presented a patient with normal radiologic and endoscopic findings. Pathology revealing frequent apoptotic bodies led to auto-GVHD as a diagnosis. Both our patients received similar courses of chemotherapy prior to autologous HSCT (four cycles of a proteasome inhibitor, lenalidomide, and dexamethasone). Our work highlights the importance of maintaining a high level of clinical suspicion for auto-GVHD in patients presenting with GI symptoms after autologous HSCT, as it is a potentially treatable pathology that may be easily confused with other conditions. Health care providers should be aware of the potential complications of auto-GVHD after autologous HSCT and should be suspicious of auto-GVHD if GI symptoms occur, especially in patients receiving immunomodulatory therapy for MM, even in the absence of gross endoscopic findings.

Minimal activity of nanoparticle albumin-bound (nab) paclitaxel in relapsed or refractory lymphomas: results of a phase-I study.

Compared with solvent-based taxanes, nanoparticle albumin-bound (nab®) paclitaxel has demonstrated improved efficacy and tolerability in several solid tumor malignancies. Studies evaluating nab paclitaxel in patients with lymphoma are lacking. In this planned phase-I/phase-II study, we sought to determine the safety and efficacy of nab-paclitaxel in patients with relapsed/refractory (R/R) lymphoma. Eligible patients (R/R to ≥2 prior systemic therapies) received weekly nab-paclitaxel on days 1, 8 and 15 every 28 days. Dosing was initiated at 100 mg/m2 with dose escalations in 25 mg/m2 increments up to 150 mg/m2 in a classic 3 + 3 design. Twenty heavily pretreated patients (median 5 prior regimens), including 65% with refractory disease, enrolled. The maximum dose tested was well tolerated and grade 3/4 hematologic adverse events (neutropenia 25%, thrombocytopenia 20% and anemia 15%) were modest. The overall response rate was 10% with two partial responses, leading to a decision to close the study prematurely.

Where does brentuximab vedotin fit into the management of patients with Hodgkin lymphoma?

Brentuximab vedotin is an antibody-drug conjugate that targets CD30 and links monomethyl auristatin E, a microtubule disrupting agent, to an anti-CD30 monoclonal antibody. A phase II study of brentuximab vedotin in relapsed/refractory classical Hodgkin lymphoma (cHL) showed an impressive overall response rate of 75 % with 34 % complete responses, and median remission duration of 20 months in complete responders. In addition, brentuximab vedotin has very modest toxicity in heavily pretreated patients, with reversible peripheral neuropathy being the most common side effect. Brentuximab vedotin received accelerated FDA approval in August 2011 for use as a salvage therapy in cHL following failure of at least two prior therapies. Brentuximab vedotin is the treatment of choice for patients relapsing after stem cell transplant and for patients refractory to standard salvage regimens pre-transplant. Because of high single-agent activity and limited side effects, brentuximab vedotin has emerged as an ideal drug to test in combination therapy for cHL. Current trials are examining the use of brentuximab vedotin in frontline combination regimens, as salvage therapy prior to stem cell transplant, and as adjuvant treatment post-transplant. Such studies will help clarify the optimal use of brentuximab vedotin in the treatment paradigm for Hodgkin lymphoma.