Donor Lymphocyte Infusion in Hematologic Malignancies--Good to be Fresh?

BACKGROUND: Donor lymphocyte infusion (DLI) has been used with variable success in a variety of hematologic malignancies. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients who were treated with DLI for persistent or relapsed disease at the Temple University Bone Marrow Transplant Unit from July 1, 1993 to December 31, 2013 to evaluate the effect of the type of DLI (fresh vs. cryopreserved) on event-free survival (EFS) and overall survival (OS). Median follow-up was 64.8 months (range, 0.3-142.6 months). RESULTS: We found that EFS and OS were similar between patients receiving cryopreserved cells and those receiving fresh DLI (median OS for cryopreserved cells, 0.39 years; median OS for fresh cells, 0.32 years; P = .793; median EFS for cryopreserved cells, 0.410 years; median EFS for fresh cells, 0.420 years; P = .4264). In the setting of relapsed disease, treatment with any chemotherapy regimen before receiving DLI did not significantly impact OS (n = 63; P = .2203) or EFS (n = 40; P = .542). A subgroup analysis limited to patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) (32 patients) showed that differences in OS and EFS between cryopreserved and fresh DLI approached significance (median OS for cryopreserved cells, 0.34 years; median OS for fresh cells, 0.17 years; P = .16; median EFS for cryopreserved cells, 0.37 years; median EFS for fresh cells, 0.094 years; P = 0.11). CONCLUSION: We conclude that the use of fresh cells versus cryopreserved cells does not have an impact on outcomes, and selected patients can achieve long-term survival with DLI for treatment of relapse after transplantation, although the overall outcomes remain dismal.

An outbreak of norovirus infection in a bone marrow transplant unit.

BACKGROUND: Norovirus is a single-stranded RNA virus belonging to the Caliciviridae family. METHODS: Our observational cohort study aimed to describe a nosocomial outbreak of norovirus on a bone marrow transplant (BMT) unit. RESULTS: Six of 8 BMT patients with increased liquid stools tested positive for norovirus: 4 had new onset diarrhea; 2 had acute exacerbations of chronic diarrhea caused by graft versus host disease. Eight non-BMT inpatients had norovirus infection, but 7 of these were community acquired; cumulative incidence rates in BMT and non-BMT units were 26% and 0.16%, respectively. In BMT patients, diarrhea (increased or new onset) lasted 6 to 33 days-durations shorter than those reported in sporadic BMT cases. All patients had private rooms and bathrooms. Five of 6 patients were on the BMT unit during their presumed incubation periods. Three were in adjacent rooms. Three nurses and 1 physician had symptoms compatible with norovirus infection, and all 4 worked while ill. The outbreak ended coincident with implementation of stricter infection control practices. CONCLUSION: Norovirus appeared to spread in a BMT unit more avidly than it did among general medical patients. Explanations include prolonged diarrhea and viral excretion, long hospital stays of infected patients, rarity of empiric contact isolation for diarrhea, routine handling of liquid stool, and a closed community of health care workers.

Spontaneous graft versus host disease occurring in a patient with multiple myeloma after autologous stem cell transplant.

Graft versus host disease (GVHD) is a common complication of allogeneic transplant. Acute GVHD primarily affects the skin, liver, and GI tract generally within the first 100 days after transplant. GVHD following an allogeneic transplant occurs as a result of donor T-cell recognition of host alloantigens. In contrast, patients undergoing ASCT are not subjected to the genetic disparity that occurs with allogeneic transplant, and in principal, should not develop this proinflammatory response. A clinical syndrome, however, has been described in patients following autologous transplant that shares the same features as GVHD occurring in recipients post-allogeneic transplant [1-3]. Previously reported cases have described skin, liver, and GI tract manifestations consistent with what is seen in allogeneic GVHD. Biopsies of the skin and GI tract mucosa have demonstrated similar histological features as well. Interestingly, the majority of reported cases seem to occur in patients with multiple myeloma undergoing consolidative ASCT. Historically, however, these patients have been described as having a relatively benign course with mild skin rash, nausea, vomiting, and/or diarrhea that is responsive to immunosuppression. In this article, we present a case of fatal, spontaneous GVHD in a patient with multiple myeloma following ASCT.

Lack of effect of donor-recipient Rh mismatch on outcomes after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: A recently published study has reported that donor-recipient Rhesus (Rh)-mismatched allogeneic hematopoietic stem cell transplantation independently led to significantly poorer survival. This suggests that donor-recipient Rh mismatching is a risk factor in allogeneic hematopoietic stem cell transplantation and should be a criterion for donor selection. STUDY DESIGN AND METHODS: To further evaluate this issue, 258 consecutive patients who underwent myeloablative or submyeloablative allogeneic hematopoietic stem cell transplantation at our institution were analyzed to determine the association between the Rh mismatch pattern and 5-year actuarial survival. Secondary endpoints analyzed were the association of donor-recipient Rh mismatch and event-free survival, transplant-related mortality, incidence of acute graft-versus-host disease (GVHD), and incidence of chronic GVHD. RESULTS: In our analysis, there were no significant associations between donor-recipient Rh mismatch pattern and overall survival, event-free survival, transplant-related mortality, incidence of acute GVHD, or incidence of chronic GVHD. On multivariate Cox proportional hazard analyses, the donor-recipient Rh mismatch pattern was not independently predictive of overall survival. CONCLUSION: Donor-recipient Rh mismatch is not a risk factor in allogeneic hematopoietic stem cell transplantation and does not affect transplant outcomes.

Mixed chimerism and graft failure following conditioning with the fludarabine and cyclophosphamide nonablative regimen; conversion to full donor chimerism.

Twenty-one patients with hematologic malignancies were treated with the fludarabine (120-125 mg/m(2)) and cyclophosphamide (120 mg/kg) nonmyeloablative conditioning regimen. Graft versus host disease (GVHD) and graft rejection prophylaxis was with tacrolimus and mycophenolate mofetil. Thirteen of the 21 patients (62%) had mixed chimerism (< or = 90% donor cells) at day 60 and 11 (52%) of these patients had mixed chimerism which persisted until day 100. Immunosuppression was discontinued in 12 of 13 patients and two of them converted to full chimerism by day 100. Eight patients received a donor lymphocyte infusion (DLI) and five of them converted to full donor chimerism with DLI alone. Two patients were given GM-CSF in addition to a DLI with conversion to full donor chimerism. Three patients (14%) had graft failure requiring a second transplant using fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)). With a median followup of 2.8 years, 15 patients are alive - one with disease and 14 with no disease. Two patients died of acute GVHD, one of chronic GVHD, and three due to progressive disease. We conclude that the nonmyeloablative fludarabine/cyclophosphamide regimen results in a significant incidence of mixed chimerism and graft rejection but is well tolerated. We suggest a more intense regimen, such as fludarabine and melphalan, be used in patients with a high risk of early disease progression to establish early engraftment and graft versus tumor effect.