Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Outcomes for Juvenile Myelomonocytic Leukemia (JMML), a 15-Year Single Center Experience

Background: JMML is a rare, highly aggressive clonal myeloproliferative disorder typically diagnosed in infants and young children.  Allogeneic HSCT is widely accepted as the standard curative therapy for JMML, but success is limited by engraftment failure or disease relapse.  Five-year overall survival ranges from 50-55%.

Objective: Evaluate our single center allogeneic HSCT outcomes for JMML.

Methods: We retrospectively reviewed data on all JMML patients who received allogeneic HSCT at our center from 1998-2013.  Data collected were age at diagnosis and HSCT, time to HSCT, sex, race/ethnicity, conditioning regimen, stem cell source, total nucleated cell dose, graft-versus-host disease (GVHD) prophylaxis, time to neutrophil (absolute neutrophil count, ANC) and platelet (PLT) engraftment, presence of acute and/or chronic GVHD, relapse, cause of death, and last time of follow-up.  Descriptive statistics were used for data analysis.

Results: Eleven patients were diagnosed with JMML and received allogeneic HSCT over the last 15 years in our center.  Median age at diagnosis was 18.6 (range 2.9-42.1) months.  Six of 11 (54.5%) were males.  Eight of 11 (72.7%) were Hispanic, 2/11 White (18.2%), and 1/11 Black (9.1%).  Median age at HSCT was 26.2 months (range 4.1-51.0) with median time to HSCT 6.1 months (range 1.2-17.1).   All received myeloablative conditioning; 8/11 (72.7%) received busulfan, cyclophosphamide, and melphalan with 5/11 (45.5%) receiving ATG.  GVHD prophylaxis was CsA+steroids (4), CsA+MMF (1), and CsA+MTX (1) and tacrolimus+MTX (5).  Stem cell source was unrelated umbilical cord blood (UCB) (7) and bone marrow (BM) (4).  UCB HLA-disparities were 5/6 (5), 4/6 (1), and 3/6 (1).  Three of 4 received matched related donor (MRD) BM while 1 received matched unrelated donor (MUD) BMT.  Median time to ANC > 500/µL was 21 days, to PLT >20,000/µL was 33 days, and to PLT >50,000/µL was 44.5 days.  One patient (UCB) had engraftment failure and received a 2nd HSCT with UCB after 200 cGy total body irradiation+fludarabine+ATG.  Acute GVHD occurred in 6/11 (54.5%), limited chronic GVHD in 2/11 (18.2%) and extensive chronic GVHD in 1/11 (9.1%).  With a median follow-up of 4.2 (range_0.1-15.2) years, 8/11 patients are alive (72.7%).  Cause of death was progression to AML (1), sinusoidal obstructive liver syndrome and HHV6 encephalitis (1) and chronic GVHD with bronchiolitis obliterans (1). 

Conclusions:  The overall survival for JMML in our center (72.7%) over the last 15 years is comparable to published data.  Despite historically poor disease-free survival, no patients have experienced recurrent JMML post-HSCT in our cohort.  We hypothesize that this observed trend toward superior survival may be due to undefined favorable characteristics in our predominantly Hispanic patient population and younger age at diagnosis.  Our experience supports the use of HLA-mismatched UCB for unrelated donor HSCT in JMML.