Abstract 3343

Poster Board III-231

Background:

lower alimentary tract mucositis (L-ATM), also known as neutropenic enterocolitis, is a complication of chemotherapy with high mortality rates. The incidence, risk factors and mortality of L-ATM remain unknown.

Purpose:

To determine the incidence, risk factors and mortality of L-ATM in a homogeneous population of patients with multiple myeloma.

Patients and Methods:

303 newly diagnosed myeloma patients (2004 - 2007) were enrolled in a protocol consisting of induction chemotherapy, tandem melphalan-based autologous stem-cell transplantation (ASCT) and consolidation. Lower -ATM was defined as grade II-IV enteritis/colitis occurring during neutropenia. All data were collected prospectively. The analysis of risk factors included body surface area (BSA), creatinine clearance (CrCl), serum albumin and other pretreatment variables. Multiple logistic regression model was used to compute adjusted odds ratio (OR) and 95% confidence intervals (CI).

Results:

47 patients (15.5%) developed L-ATM during 1528 chemotherapy cycles (including 536 ASCT). BSA < 2 m2 (OR 2.853; 95% CI 1.232, 6.607; p = 0.0144) and CrCl <60ml/min (OR 3.089; 95% CI 1.176, 8.114; p = 0.0221) increased the risk for L-ATM while higher serum albumin was protective (OR 0.695; 95% CI 0.517, 0.936; p = 0.0167). No L-ATM-related death was observed.

Conclusions:

Lower-ATM is not uncommon among myeloma patients undergoing multiple cycles of chemotherapy but does not contribute to mortality. The risk for L-ATM is determined by lower values of BSA, renal function and serum albumin. These findings have significant implications for the study and management of L-ATM in patients undergoing chemotherapy.

Multivariate analysis: Risk factors for lower alimentary tract mucositis (L-ATM)

Treatment stageVariablesControl group¤L-ATM
BaselineN (%)N (%)OR (95% CI)p- value
 ALB (g/dL), unit = 0.5 39.97 ± 5.12 37.79 ± 6.01 0.695 (0.517, 0.936) 0.0167 
 BSA (<2.0 m2) 132 (61.97) 39 (82.98) 2.853 (1.232, 6.607) 0.0144 
 e-CrCl (<60 ml/min) 31 (14.55) 13 (27.66) 1.534 (0.697, 3.375) 0.2880 
Induction cycle 2      
 ALB (g/dL), unit = 0.5 36.86 ± 4.05 33.00 ± 3.22 0.347 (0.129, 0.934) 0.0362 
 BSA (<2.0 m2) 186 (67.39) 3 (50.00) 0.567 (0.105, 3.073) 0.5106 
 e-CrCl (<60 ml/min) 34 (12.32) 1 (16.67) 1.469 (0.153, 14.09) 0.7390 
Transplant 1      
 ALB (g/dL), unit = 0.5 38.60 ± 4.11 35.53 ± 3.16 0.462 (0.248, 0.863) 0.0154 
 BSA (<2.0 m2) 165 (64.71) 15 (88.24) 4.130 (0.874, 19.53) 0.0735 
 e-CrCl (<60 ml/min) 21 (8.24) 6 (35.29) 3.688 (1.093, 12.44) 0.0354 
Transplant 2      
 ALB (g/dL), unit = 0.5 38.65 ± 4.27 36.96 ± 4.45 0.748 (0.470, 1.190) 0.2207 
 BSA (<2.0 m2) 139 (64.65) 24 (92.31) 5.906 (1.339, 26.05) 0.0190 
 e-CrCl (<60 ml/min) 19 (8.84) 5 (19.23) 1.586 (0.505, 4.987) 0.4299 
Transplants 1 +2(N=285)      
 ALB (g/dL), unit = 0.5 38.79 ± 4.23 36.41 ± 2.88 0.489 (0.304, 0.787) 0.0032 
 BSA (<2.0 m2) 141 (62.39) 33 (89.19) 5.433 (1.779, 16.59) 0.0030 
 e-CrCl (<60 ml/min) 16 (7.08) 10 (27.03) 3.089 (1.176, 8.114) 0.0221 
Consolidation cycles 1+2      
 ALB (g/dL), unit = 0.5 38.10 ± 3.78 37.86 ± 4.06 0.899 (0.367, 2.201) 0.8151 
 BSA (<2.0 m2) 130 (65.99) 7 (100.0) . . 
 e-CrCl (<60 ml/min) 15 (7.61) 2 (28.57) 3.162 (0.571, 17.51) 0.1874 
Treatment stageVariablesControl group¤L-ATM
BaselineN (%)N (%)OR (95% CI)p- value
 ALB (g/dL), unit = 0.5 39.97 ± 5.12 37.79 ± 6.01 0.695 (0.517, 0.936) 0.0167 
 BSA (<2.0 m2) 132 (61.97) 39 (82.98) 2.853 (1.232, 6.607) 0.0144 
 e-CrCl (<60 ml/min) 31 (14.55) 13 (27.66) 1.534 (0.697, 3.375) 0.2880 
Induction cycle 2      
 ALB (g/dL), unit = 0.5 36.86 ± 4.05 33.00 ± 3.22 0.347 (0.129, 0.934) 0.0362 
 BSA (<2.0 m2) 186 (67.39) 3 (50.00) 0.567 (0.105, 3.073) 0.5106 
 e-CrCl (<60 ml/min) 34 (12.32) 1 (16.67) 1.469 (0.153, 14.09) 0.7390 
Transplant 1      
 ALB (g/dL), unit = 0.5 38.60 ± 4.11 35.53 ± 3.16 0.462 (0.248, 0.863) 0.0154 
 BSA (<2.0 m2) 165 (64.71) 15 (88.24) 4.130 (0.874, 19.53) 0.0735 
 e-CrCl (<60 ml/min) 21 (8.24) 6 (35.29) 3.688 (1.093, 12.44) 0.0354 
Transplant 2      
 ALB (g/dL), unit = 0.5 38.65 ± 4.27 36.96 ± 4.45 0.748 (0.470, 1.190) 0.2207 
 BSA (<2.0 m2) 139 (64.65) 24 (92.31) 5.906 (1.339, 26.05) 0.0190 
 e-CrCl (<60 ml/min) 19 (8.84) 5 (19.23) 1.586 (0.505, 4.987) 0.4299 
Transplants 1 +2(N=285)      
 ALB (g/dL), unit = 0.5 38.79 ± 4.23 36.41 ± 2.88 0.489 (0.304, 0.787) 0.0032 
 BSA (<2.0 m2) 141 (62.39) 33 (89.19) 5.433 (1.779, 16.59) 0.0030 
 e-CrCl (<60 ml/min) 16 (7.08) 10 (27.03) 3.089 (1.176, 8.114) 0.0221 
Consolidation cycles 1+2      
 ALB (g/dL), unit = 0.5 38.10 ± 3.78 37.86 ± 4.06 0.899 (0.367, 2.201) 0.8151 
 BSA (<2.0 m2) 130 (65.99) 7 (100.0) . . 
 e-CrCl (<60 ml/min) 15 (7.61) 2 (28.57) 3.162 (0.571, 17.51) 0.1874 
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Pre-treatment characteristics of 303 myeloma patients: Lower alimentary tract mucositis (LATM) vs. controls

All patients N=303Control group ¤ N=213LATM N=47P-valueμ
CMV IgG positive, N (%) 190 (62.7) 139 (65.3) 25 (53.2) 0.1345 
Body Surface Area (BSA)† 
Median, m2 1.88 1.9 1.80 0.0253 
Range, m2 1.41-2.56 1.41 - 2.56 1.48 - 2.21  
< 2.01 m2 201 (66.3) 132 (62.0) 39 (83.0) 0.0063 
>= 2.01 m2 102 (33.7) 81 (38.0) 8 (17.0)  
Melphalan dose for transplant cycles 
Transplant 1 N=285 N=255 N=17  
Median, mg/kg 4.49 4.42 4.58 0.2329 
Range, mg/kg 2.00-6.82 2.00 - 6.53 3.10 - 6.82  
Transplant 2 N=251 N=215 N=26  
Median, mg/kg 4.50 4.47 4.94 0.0250 
Range, mg/kg 2.41-6.58 2.41 - 6.58 3.05 - 6.11  
Serum Albumin 
Median, g/dL 4 4 3.9 0.0207 
Range, g/dL 2.1-5.3 2.5 – 5.3 2.1 - 4.9  
Estimated creatinine clearance 
Median, ml/min 93.8 95.2 87.7 0.1463 
Range, ml/min 9.0 -245.7 9.0 - 245.7 9.9 - 172.4  
<60 ml/min 49 (16.2) 31 (14.6) 13 (27.7) 0.0505 
≥60 ml/min 254 (83.8) 182 (85.5) 34 (72.3)  
All patients N=303Control group ¤ N=213LATM N=47P-valueμ
CMV IgG positive, N (%) 190 (62.7) 139 (65.3) 25 (53.2) 0.1345 
Body Surface Area (BSA)† 
Median, m2 1.88 1.9 1.80 0.0253 
Range, m2 1.41-2.56 1.41 - 2.56 1.48 - 2.21  
< 2.01 m2 201 (66.3) 132 (62.0) 39 (83.0) 0.0063 
>= 2.01 m2 102 (33.7) 81 (38.0) 8 (17.0)  
Melphalan dose for transplant cycles 
Transplant 1 N=285 N=255 N=17  
Median, mg/kg 4.49 4.42 4.58 0.2329 
Range, mg/kg 2.00-6.82 2.00 - 6.53 3.10 - 6.82  
Transplant 2 N=251 N=215 N=26  
Median, mg/kg 4.50 4.47 4.94 0.0250 
Range, mg/kg 2.41-6.58 2.41 - 6.58 3.05 - 6.11  
Serum Albumin 
Median, g/dL 4 4 3.9 0.0207 
Range, g/dL 2.1-5.3 2.5 – 5.3 2.1 - 4.9  
Estimated creatinine clearance 
Median, ml/min 93.8 95.2 87.7 0.1463 
Range, ml/min 9.0 -245.7 9.0 - 245.7 9.9 - 172.4  
<60 ml/min 49 (16.2) 31 (14.6) 13 (27.7) 0.0505 
≥60 ml/min 254 (83.8) 182 (85.5) 34 (72.3)  

Control group ¤: patients who did not develop enterocolitis (neutropenic or Clostridium difficile colitis (CDI)) during any cycle of therapy. 43 patients with CDI were excluded from analysis.

† BSA cut off at 2 m2 is based on the highest tertile of the control group

μ Fisher's exact test used for categorical variables, Wilcoxon rank sum test for continuous variables.

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
chemotherapy regimen, gastrointestinal tract, mucositis, multiple myeloma, neutropenic enterocolitis, transplantation, serum albumin, autologous stem cell transplant, creatinine clearance, melphalan

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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