Sagun D. Goyal

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/m2 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.

Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study.

The appropriate induction therapy before and the role of maintenance therapy after auto-SCT for patients with multiple myeloma remain areas of active investigation. We conducted a study in 40 patients with bortezomib given sequentially pre-auto-SCT and as maintenance therapy post auto-SCT. Pre-transplant bortezomib was administered for two cycles followed by high-dose melphalan 200 mg/m2 with auto-SCT of G-CSF-mobilized PBMCs. Post transplant bortezomib was administered weekly for 5 out of 6 weeks for six cycles. No adverse effects were observed on stem cell mobilization or engraftment. An overall response rate of 83% with a CR+very good partial remission (VGPR) of 50% was observed with this approach. Three-year Kaplan–Meier estimates of disease-free survival and overall survival (OS) were 38.2 and 63.1%, respectively. Bortezomib reduced CD8+ cytotoxic T cell and CD56+ natural killer cell PBL subsets and was clinically associated with high rates of viral reactivation to varicella zoster.

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 µm2/s, 21.3 cm2 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. Copyright

Allogeneic hematopoietic cell transplant for AML: no impact of pre-transplant extramedullary disease on outcome.

The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91–1.09), LFS (0.98, 0.89–1.09), TRM (relative risk 0.92, 95% CI 0.80–1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92–1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.

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

Abstract 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.