Alison W. Loren

Post-transplant lymphoproliferative disorder: a review

Summary:Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of Epstein–Barr virus-related (EBV) clinical diseases, from a benign mononucleosis-like illness to a fulminant non-Hodgkins lymphoma. In the setting of hematopoietic stem cell transplantation, PTLD is an often-fatal complication occurring relatively early after transplant. Risk factors for the development of PTLD are well established, and include HLA-mismatching, T-cell depletion, and the use of antilymphocyte antibodies as conditioning or treatment of graft-versus-host disease. Early recognition of PTLD is particularly important in the SCT setting, because PTLD in these patients tends to be rapidly progressive. Familiarity with the clinical features of PTLD and a heightened level of suspicion are critical for making the diagnosis. Surveillance techniques with EBV antibody titers and/or polymerase chain raction (PCR) may have a role in some high-risk settings. Immune-based therapies such as monoclonal anti-B-cell antibodies, interferon-α, and EBV-specific donor T cells, either as treatment for PTLD or as prophylaxis in high-risk patients, represent promising new directions in the treatment of this disease.

Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation

We conducted a retrospective analysis of 50 lymphoma patients (Hodgkins disease and non-Hodgkins lymphoma) who had an 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan after at least two cycles of salvage chemotherapy and before autologous stem cell transplantation (ASCT) at our institution. The patients were categorized into FDG-PET negative (N=32) and positive (N=18) groups. The median follow-up after ASCT was 19 months (range: 3–59). In the FDG-PET-negative group, the median progression-free survival (PFS) was 19 months (range: 2–59) with 15 (54%) patients without progression at 12 months after ASCT. The median overall survival (OS) for this group was not reached. In the FDG-PET-positive group, the median PFS was 5 months (range: 1–19) with only one (7%) patient without progression at 12 months after ASCT. The median OS was 19 months (range: 1–34). In the FDG-PET-negative group, chemotherapy-resistant patients by CT-based criteria had a comparable outcome to those with chemotherapy-sensitive disease. A positive FDG-PET scan after salvage chemotherapy and prior ASCT indicates an extremely poor chance of durable response after ASCT.

Trisomy 8 in an allogeneic stem cell transplant recipient representative of a donor-derived constitutional abnormality.

Trisomy 8 is a common cytogenetic abnormality in myeloid malignancies. It can also be present constitutionally and is associated with a wide range of phenotypes. We report a case of a 20‐year‐old woman with acute myelogenous leukemia associated with the 11q23/MLL translocation who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a healthy, unrelated 26‐year‐old female. Cytogenetics on a bone marrow biopsy and aspirate performed 71 days after transplant to evaluate pancytopenia identified trisomy 8 in 6 of 7 cells examined. The bone marrow was hypocellular but normal by morphology and flow cytometry. Fluorescent in situ hybridization (FISH) for the original 11q23/MLL translocation was negative. Chimerism analysis using multiplex polymerase chain reaction to amplify an informative short tandem repeat demonstrated 97% donor cells. These findings were confirmed by repeat bone marrow biopsies at Day 110 after transplant and 1 year after transplant. With resolution of comorbid illness, the patients peripheral blood counts recovered and remained normal at 1 year after HSCT. FISH analysis of a cryopreserved sample of the donor graft showed trisomy 8 in 120 of 200 cells examined. This represents the first reported case of a person with constitutional trisomy 8 mosaicism serving as a stem cell donor. The case illustrates the importance of identifying donor‐derived constitutional abnormalities to avoid the assumption that these cytogenetic abnormalities after HSCT are representative of malignant disease. Am. J. Hematol., 2008.

Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after autologous stem cell transplant in the current era of novel therapeutics: A retrospective analysis

Patients with relapsed/refractory Hodgkin lymphoma (RR‐HL) who progress or relapse following autologous stem cell transplantation (ASCT) have historically had a poor prognosis. Several novel agents, particularly brentuximab vedotin, have shown efficacy in this setting. However, there remains a paucity of data characterizing outcomes outside of clinical trials and how these novel agents have impacted prognosis in general population of patients with RR‐HL. Here, we conducted a retrospective analysis to evaluate outcomes in 87 patients with RR‐HL with relapse post‐ASCT. Treatment with novel agents (including brentuximab vedotin) was associated with significant improvement in median overall survival (OS) compared to patients who did not receive novel agents (85.6 vs 17.1 months; P < .001). Additional factors associated with improved OS in univariate analysis include treatment with radiation therapy post‐ASCT (34.1 vs 17.0 months; P = .015), chemosensitivity (i.e., relapsed compared to primary refractory disease; 51.8 vs 25.6 months; p = 0.013), initial response to ASCT (i.e., CR/PR compared to SD/PD; 46.1 vs 20.4 months; P = .011), and transplantation in 2010 and later compared to prior to 2010 (not reached vs 24.5 months; P = .025). The current study demonstrates markedly improved OS in RR‐HL patients treated with novel therapeutics and lends “real world” credence to the role of these agents in improving outcomes in the current era.

Implementation of an Advanced Practice Provider Service on an Allogeneic Stem Cell Transplant Unit: Impact on Patient Outcomes.

Allogeneic stem cell transplantation (ASCT) is a complex medical procedure for some patients with hematologic malignancies. Most ASCTs occur at academic centers where either medical residents (house staff [HS]) or advanced practice providers (APPs) provide daily care. As a result of increasing work-hour regulations, APPs have assumed greater responsibilities, including those traditionally held by HS. In this study we evaluate ASCT patient outcomes by inpatient provider service. A retrospective, single-center chart review of ASCT patients was performed. ASCT patients admitted to an HS service from May 2011 to May 2012 (N = 86) were compared with ASCT patients admitted to a newly formed APP service from October 2012 to October 2013 (N = 81). As part of a secondary sensitivity analysis, we compared ASCT patients on the APP service to a subset of ASCT patients admitted to the HS service also from October 2012 to October 2013 (n = 27). Our primary outcomes were 100-day survival and relapse-free survival rates. Additional outcomes included length of stay (LOS), inpatient complications, and ordering behavior. Our primary pre- and post-analyses found no differences in 100-day overall survival and 100-day relapse-free survival rate between the services. The rate of pneumonia was lower on the APP service (15% versus 28%, P = .04), with no significant differences in other infectious complications. HS ordered more blood cultures (6.7 versus 4.2, P = .03) per patient than the APP service. There was no difference in LOS, readmission rates, or inpatient mortality. With regards to our secondary sensitivity analysis, no differences were found in 100-day overall survival and 100-day relapse-free survival rates between the services. There was a decreased LOS on the APP service (29.4 versus 37.2 days, P = .01). HS ordered more blood cultures (9.3 versus 4.2, P < .01) and more radiological films (8.1 versus 5.2, P = .05) per patient than the APP service. This increased ordering and LOS was associated with an increase in mean hospital charges on the HS service (P = .04). ASCT patients on an APP service had similar 100-day outcomes as those on the HS service. In the setting of limited resources, APPs are potential alternative providers for complex transplant inpatients.