Identification of Prognostic Features Associated with Survival in Juvenile Myelomonocytic Leukemia (JMML) Open Access

Sabnis, Himalee (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/dr26xx537?locale=en
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Abstract

Juvenile Myelomonocytic Leukemia is a rare myeloproliferative disorder of childhood with a five year overall survival ranging between 52-64%. Allogeneic stem cell transplantation is regarded as the only curative treatment modality but up to 50% of all transplant recipients will relapse within the first year after transplantation. We studied 114 JMML patients enrolled on the North American JMML Project (NAJP) registry to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) affected survival and to determine clinical and laboratory parameters that influence overall survival (OS). The two-year overall survival of all patients enrolled was 47% ± 0.05 with a median survival time of 449 days. We found that HSCT significantly improved the two-year survival of JMML patients (38% ± 0.07 versus 52% ± 0.06, p-value 0.024). Age at diagnosis, gender, lung disease, Neurofibromatosis type 1 (NF1), transplantation status, white blood count, platelet count, fetal hemoglobin levels and monosomy 7 were assessed as univariate predictors for OS in a Cox Proportional Hazards Model. Age at diagnosis >24 months (HR 1.98, 95% CI 1.04 - 3.76, p-value 0.03), presence of lung disease (HR 4.37, 95% CI 1.77 - 10.8, p-value 0.001), and platelet count <40K/µl (HR 0.46, 95% CI 0.24 - 0.86, p-value 0.01) were found to be adverse risk factors for overall survival in the multivariate model. Sub-analysis of the transplanted patients was done using the above mentioned covariates in addition to specific covariates applicable only to transplanted patients. Transplantation covariates that were studied included age at transplant, wait time between study enrollment to transplant and type of donor source (related versus unrelated). Analysis showed that presence of NF1 (HR 0.17, 95% CI 0.04 - 0.76, p-value 0.02), high white blood count >50 K/µl at diagnosis (HR 0.31, 95% CI 0.12 - 0.80, p-value 0.01) and wait time >120 days (HR 0.34, 95% CI 0.15 - 0.74, p-value 0.006) were favorable predictors for overall survival in patients that received a hematopoietic stem cell transplant. Future studies should examine the role of therapy for relapsed or recurrent disease in JMML as well as the effects of transplant regimens and transplant complications on overall survival.

Table of Contents

INTRODUCTION.. 1
BACKGROUND.. 4
METHODS. 8
RESULTS. 12
DISCUSSION.. 17
CONCLUSION.. 21
REFERENCES. 22
TABLES AND FIGURES. 25
TABLE 1: Characteristics of patients on North American JMML Project (NAJP) registry 25
TABLE 2: Clinical characteristics of patients on North American JMML Project (NAJP) registry 26
TABLE 3: Laboratory characteristics of patients on North American JMML Project (NAJP) registry 27
TABLE 4: Comparison of clinical characteristics present at diagnosis between patients who received hematopoietic stem cell transplant versus no transplant 28
TABLE 5: Comparison of laboratory characteristics present at diagnosis between patients who received hematopoietic stem cell transplant versus no transplant 29
FIGURE 1: Overall survival of all patients (n=114). 30
FIGURE 2: Two year overall survival of all patients depending on transplantation status 31
FIGURE 3: One year overall survival of all patients on NAJP registry depending on transplantation status after accounting for early mortality (within 138 days of presentation). 32
TABLE 6: Univariate analysis of clinical and laboratory parameters in overall survival (n=114) 33
TABLE 7A: Interaction between NF1 and transplantation status. 34
TABLE 7B: Interaction between lung disease and transplantation status. 34
TABLE 8: Multivariate analysis of clinical and laboratory parameters in overall survival 35
FIGURE 4: Two year overall survival of all patients that received hematopoietic stem cell transplantation depending on donor source. 36
TABLE 9: Univariate analysis of clinical and laboratory parameters in overall survival within patients that underwent hematopoietic stem cell transplantation. 37
TABLE 10: Multivariate analysis of clinical and laboratory parameters in overall survival of patients that underwent hematopoietic stem cell transplantation. 38

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