Paper: Engraftment Syndrome Has Distinct Biology Compared with Graft Versus Host Disease

Pediatric BMT Program

155 A-F (Salt Palace Convention Center)

Pooja Khandelwal, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Sabine Mellor-Heinke, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Stella M. Davies, MBBS, PhD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Michael Grimley, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Jack Bleesing, MD, PhD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Michael Jordan, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Sonata Jodele, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Rebecca A Marsh, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Parinda A. Mehta, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Kasiani Myers, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Najibah Rehman, MPH , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Kristi Smiley, MS , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Joyce Villanueva, MT MBA/HCM , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Alexandra Filipovich, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Introduction

The biology of engraftment syndrome (ES) is poorly understood and the degree of overlap with GVHD is unclear.

Methods

To better understand ES, plasma cytokine profiles were evaluated in 52 consecutive pediatric allogeneic bone marrow transplant recipients prior to transplant, on the day of stem cell infusion and weekly until day+100. Patients were divided into three groups, those with isolated engraftment syndrome (n=4), acute graft versus host disease without prior ES (n=12) and with neither engraftment syndrome nor acute graft versus host disease (n=32). Cytokine values were expressed as mean fold increase from pre transplant values.

Results

Median age of recipients was 6.7 years (range 0.6-19.4). ES was observed a median of 12.5 days (range 11-15) after transplant, while aGVHD was diagnosed at median of 55 days (range 19-95 days) after transplant. MCP-1 and MIP1b were significantly elevated in patients with ES during the first two weeks, while remaining unchanged or reduced in either of the other 2 cohorts. Moreover, while various cytokines were found to be elevated in patients who developed aGVHD, the degree of elevation was significantly exaggerated in patients with isolated ES during 4 weeks post-transplant. (See table)

Conclusion

MCP-1 and MIP1b are elevated specifically in ES suggesting a separate biology from GVHD. In addition, the degree of elevation of pro-inflammatory cytokines is markedly greater in children with ES compared to those with GVHD.

Figure 1. MIP1b and MCP1 in patients with ES, aGVHD and neither GVHD nor ES.

Cytokine

Neither ES nor GVHD ( Mean fold increase from pre transplant value)

GVHD
( Mean fold increase from pre transplant values)

ES
( Mean fold increase from pre transplant values)

P value
(ES vs GVHD)

IL1b

0

2

36

<0.01

IL4

2

5

40

<0.001

IL7

8

6

138

<0.01

IL12

14

4.6

108

<0.01

IL13

2.8

3

62

<0.01

Table 1. Cytokine profiles in ES, aGVHD and patients with neither ES nor GVHD at 4 weeks after transplant

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Cytokine	Neither ES nor GVHD ( Mean fold increase from pre transplant value)	GVHD ( Mean fold increase from pre transplant values)	ES ( Mean fold increase from pre transplant values)	P value (ES vs GVHD)
IL1b	0	2	36	<0.01
IL4	2	5	40	<0.001
IL7	8	6	138	<0.01
IL12	14	4.6	108	<0.01
IL13	2.8	3	62	<0.01

94 Engraftment Syndrome Has Distinct Biology Compared with Graft Versus Host Disease