Allogeneic Hematopoietic Cell Transplantation for Therapy-Related Myeloid Leukemia following Orthotopic Cardiac Transplantation.

Therapy-related myeloid neoplasm (t-MN) is a subtype of acute myeloid leukemia with adverse cytogenetics and poor overall prognosis despite intensive induction chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT). It is increasingly recognized as a late complication of chronic immunosuppression in patients who have received solid organ transplantation. In this paper, we describe a case of t-MN following orthotopic cardiac transplantation and its treatment with allo-HCT. We discuss molecular and biological challenges and considerations in double solid organ and bone marrow transplantation and review similar cases at our institution. Our experience suggests general feasibility and safety of allo-HCT in patients who have received solid organ transplantation.

Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions.

We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34(+) stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P = .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800.

Treatment of therapy-related myeloid neoplasms with high-dose cytarabine/mitoxantrone followed by hematopoietic stem cell transplant.

Few clinical protocols have focused on patients with therapy-related myeloid neoplasms (t-MN). Therefore, we enrolled 32 patients with previously untreated t-MN on a clinical trial testing the effectiveness of a unified induction regimen of high-dose cytarabine and mitoxantrone. The complete remission (CR) rate was 66% (95% CI 47-81%) and the partial remission (PR) rate was 16% (95% CI 5-33%), for an overall response rate of 82%. Day 30 treatment mortality was 9% (3/32), and the most serious induction toxicity was cardiac dysfunction. Among the patients with CR, 13 (62%) received consolidation therapy using an allogeneic hematopoietic cell transplant (HCT), four (21%) received an autologous HCT, and three (16%) received further chemotherapy. We observed long-term disease-free survival in patients who received all three types of consolidation therapy. The remission induction of high-dose cytarabine and mitoxantrone for t-MN is a well-tolerated efficacious combination, which allows aggressive consolidation and long-term disease-free survival.

Pretreatment C-reactive protein is a predictor for outcomes after reduced-intensity allogeneic hematopoietic cell transplantation.

We tested the independent prognostic impact of 2 commonly used biomarkers, C-reactive protein (CRP) and interleukin (IL)-6, on the outcomes of allogeneic hematopoietic cell transplantation (HCT). Consecutive patients who underwent a uniform reduced-intensity conditioning (RIC) regimen of fludarabine (Flu), melphalan (Mel), and alemtuzumab were evaluated retrospectively. Cryopreserved serum samples drawn before the RIC were available to measure CRP levels in 81 patients and IL-6 levels in 79 patients. Patients with CRP levels above the median of 18.5 mg/L had significantly more grade 3-4 hepatic toxicity (P=.01), longer HCT hospital stay (P=.005), more acute graft-versus-host disease (aGVHD) (P=.003), greater nonrelapse mortality (NRM) (P=.01), and inferior overall survival (OS; P=.02). Higher baseline CRP showed no significant correlation with grade 3-4 infectious toxicity (P=.09). In contrast to CRP, pre-HCT IL-6 levels above the median of 78.3 pg/mL did not confer a statistically significant increased risk of toxicity or mortality. An elevated HCT comorbidity index (HCT-CI) did not predict for any measure of HCT morbidity. After adjustment for disease status, comorbidity, performance status, and age, elevated CRP concentration remained predictive of NRM. These data require confirmation in non-T cell-depleted conditioning regimens. If validated, they suggest that preconditioning CRP holds promise for enhancing estimates of transplantation tolerance.