Abstract 5226

Background

Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder with overlapping features between myelodysplastic syndromes and myeloproliferative neoplasms.  Allogeneic stem-cell transplant (SCT) is considered to be a potentially curative option (Eur J Haematol. 2013; 90:355); with karyotype and comorbidity index (CI) being independent prognostic factors.  The role of newer CMML prognostic models remains to be elucidated.  We carried out this study to analyze the predictive value of the Mayo model (Leukemia 2013; 27:1504) in assessing transplant outcomes for patients with CMML.

Methods

After due IRB approval, 25 patients with WHO-defined CMML that underwent allo-SCT at Mayo Clinic from 1992 through 2013 were identified. All patients underwent bone marrow examination and cytogenetic evaluation at diagnosis. Clinical features including status at transplant, graft-versus-host disease (GVHD) prophylaxis, donor-recipient HLA-matching, donor-recipient blood types and CMV status were documented. Patients were evaluated for development of GVHD, disease relapse, remission status, and death from all causes. We evaluated the prognostic relevance of clinical and laboratory parameters including those previously identified by the MDAPS (Blood 2002;99:840), Spanish cytogenetic stratification (Haematologica 2011;96:375), and the recently described Mayo model

Results

Among 25 study patients, 14 (56%) were males and 15 (60%) had WHO defined CMML-1 (6-symptomatic/transfusion dependent, 3-monosomy 7).  The median age at transplant was 51 years (range, 18-66 years). Graft sources included: 19 (76%) peripheral blood, 5 (20%) bone marrow, and 1 (4%) double umbilical cord blood. Ten (40%) patients received a reduced intensity conditioning.  At last follow up, 15 (60%) deaths were documented while the remainders are alive and disease free. There were six (25%) post-transplant relapses all resulting in mortality.  The 5-year OS was 42% and the 5-year non relapse mortality was 35%.  Based on the Mayo model, 15 (60%) patients received a high-risk prognostication, 6 (24%) were intermediate and 3 (12%) were low.

In an univariate analysis that included: demographics, blood counts at diagnosis and transplant, WHO classification (p=0.19), Spanish karyotypic stratification (p=0.67), prognostication according to the MDAPS (p=0.35) and Mayo model, disease status at transplant, SCT comorbidity index (p=0.06), graft sources, transplant conditioning regimens (p=0.08), development of acute (p=0.64) and chronic GVHD (p=0.06); thrombocytopenia at diagnosis (p=0.04), disease status at transplant (p=0.02), and a high risk prognostication using the  Mayo  model (p=0.01) were statistically significant. On a multivariable analysis only high risk prognostication by the Mayo model (p=0.02) retained its negative prognostic impact. In an univariate analysis for relapse-free survival, risk stratification by the Spanish cytogenetic system (p=0.04) and the Mayo model were prognostic (p=0.01), with the high risk prognostication by the Mayo model retaining its negative prognostic impact (p=0.01).

Conclusions

  Allogeneic SCT remains a viable treatment option for patients with CMML. The Mayo model serves as a valuable tool, helping with the identification of high risk CMML patients.  These patients seem to benefit from allo-SCT in comparison to non-transplant therapeutic options.   Given the smaller sample size, validation in a larger patient cohort is needed.

Table 1

Clinical Parameters and Outcomes among Mayo Model-Defined “High-Risk” CMML Patients

Age Gender WHO diagnosis MD Anderson category Spanish Risk category Karyotype [20] Reduced Intensity Y/N Chronic GVHD  Status
62  M  CMML-2  Interm-1  Interm.  46,XY,idem,del(20)(q11.2q13.1)  N  severe  Dead  
59  F  CMML-1  Low  Low  46,XX  Y     Alive  
26  F  CMML-1  High  High  45,XX,-7  N  severe  Dead  
51  F  CMML-2  Interm-2  Low  46,XX  N  severe  Alive  
66  M  CMML-2  High  Low  46,XY  Y  severe  Alive  
43  F  CMML-1  Interm-2  Low  46,XX  N  mild  Dead  
43  F  CMML-1  Interm-1  Low  46,XX  N     Dead  
57  M  CMML-2  Interm-2  High  45,XY,-7  Y  severe  Dead  
41  F  CMML-2  High  Interm.  46,XX,inv(2)(p23q13)  N     Alive  
45  M  CMML-2  Low  Interm.  46,XY  N     Alive  
59  M  CMML-2  Interm-2  Interm.  46,XY  Y  moderate  Alive  
50  F  CMML-1  Interm-1  Low  46,XX,trans(1,3)  N  severe  Dead  
64  F  CMML-1  Interm-2  Interm.  46,XX  Y  mild  Dead  
52  M  CMML-1  Low  Interm.  46,XY  N     Dead  
18  M  CMML-2  High  High  44,Y,-7,-8,  Y     Alive  
Age Gender WHO diagnosis MD Anderson category Spanish Risk category Karyotype [20] Reduced Intensity Y/N Chronic GVHD  Status
62  M  CMML-2  Interm-1  Interm.  46,XY,idem,del(20)(q11.2q13.1)  N  severe  Dead  
59  F  CMML-1  Low  Low  46,XX  Y     Alive  
26  F  CMML-1  High  High  45,XX,-7  N  severe  Dead  
51  F  CMML-2  Interm-2  Low  46,XX  N  severe  Alive  
66  M  CMML-2  High  Low  46,XY  Y  severe  Alive  
43  F  CMML-1  Interm-2  Low  46,XX  N  mild  Dead  
43  F  CMML-1  Interm-1  Low  46,XX  N     Dead  
57  M  CMML-2  Interm-2  High  45,XY,-7  Y  severe  Dead  
41  F  CMML-2  High  Interm.  46,XX,inv(2)(p23q13)  N     Alive  
45  M  CMML-2  Low  Interm.  46,XY  N     Alive  
59  M  CMML-2  Interm-2  Interm.  46,XY  Y  moderate  Alive  
50  F  CMML-1  Interm-1  Low  46,XX,trans(1,3)  N  severe  Dead  
64  F  CMML-1  Interm-2  Interm.  46,XX  Y  mild  Dead  
52  M  CMML-1  Low  Interm.  46,XY  N     Dead  
18  M  CMML-2  High  High  44,Y,-7,-8,  Y     Alive  
View Large
Disclosures:

No relevant conflicts of interest to declare.

Topics:
allogeneic stem cell transplant, leukemia, myelomonocytic, chronic, transplantation, graft-versus-host disease, allopurinol, graft-versus-host disease, chronic, karyotype determination procedure, tissue transplants, bone marrow examination, disease remission

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
Sign in via your Institution