What Is Engraftment Syndrome?

Stem cells

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In This Article

Engraftment syndrome is a complication that can occur after a bone marrow transplant, a procedure also known as hematopoietic stem cell transplant.

Engraftment is the part of the transplant process when the body accepts transplanted bone marrow or stem cells and begins to produce new blood cells. Engraftment syndrome is an inflammatory response in the body that is not fully understood, though it has been known to occur after both main types of a hematopoietic stem cell transplant: autologous (transplant from self) and allogeneic (from another, often related donor).

Engraftment syndrome symptoms may mimic those of graft versus host disease (GVHD), when donated bone marrow or stem cells deem the recipient's cells foreign and attack.

Causes

The exact cause of engraftment syndrome is not known, but it is thought that a mix of certain cell signals and interactions that cause an overproduction of pro-inflammatory cytokines (part of the immune response) may have a major role.

The process is complex and involves several potential factors. For example, fluid in the lungs is thought to be caused by cell signals that cause tiny capillaries to become leaky.

Because engraftment syndrome is seen with different types of transplant donors and different types of transplants, and since the syndrome may be distinct from GVHD and coincides with recovery of the white cells known as granulocytes, researchers reason that it is likely to be mediated by activated white blood cells and pro-inflammatory cell signals.

Symptoms

There are several possible signs and symptoms of engraftment syndrome, some of which a patient will not be able to detect themselves.

Most symptoms of engraftment syndrome are mild, although some can be severe and even life-threatening. In its most extreme form, the term aseptic shock syndrome has been used, meaning that there is a collapse of the circulatory system and multi-organ failure.

It's helpful to review signs and symptoms in the context of diagnostic criteria set out by Thomas R. Spitzer, MD, a clinical researcher at the Bone Marrow Transplant Program at Massachusetts General Hospital in Boston, Massachusetts in 2001. Dr. Spitzer published the seminal paper on engraftment syndrome, and his criteria have been used to make diagnoses ever since.

Major criteria:

  • Temperature greater than or equal to 100.9 degrees F with no identifiable infectious cause
  • Red rash covering more than 25% of the body that's not attributable to an infection or medication
  • Excess fluid in the lungs (pulmonary edema) not caused by a heart problem, as seen on imaging scans, and low oxygen in the blood (hypoxia)

Minor criteria:

  • Liver dysfunction with certain parameters (bilirubin greater than or equal to 2 mg/dL or the enzyme transaminase greater than or equal to 2 times normal)
  • Kidney insufficiency (serum creatinine greater than or equal to 2x baseline)
  • Weight gain (greater than or equal to 2.5% of pre-transplant body weight)
  • Temporary confusion or brain abnormalities unexplained by other causes

Diagnosis

Diagnosis, based on the above, requires all three major criteria or two major criteria and one or more minor criteria within 96 hours (four days) of engraftment.

While Dr. Spitzer's criteria have been widely used to diagnose engraftment syndrome (and he published a follow-up in 2015), another researcher, Angelo Maiolino, MD, established slightly different diagnostic criteria in 2004. While they also include fever, rash, and pulmonary edema, with the addition of diarrhea, the specifics differ enough to have sparked debate among experts.

That said, a diagnosis of engraftment syndrome typically is made based on these collective criteria, which are established from the patient's visible symptoms and potential blood tests for liver and kidney function.

Treatment

In many cases, engraftment syndrome resolves on its own and requires no treatment.

When treatment is necessary, the condition appears to be responsive to corticosteroid (dexamethasome) treatment for as long as the symptoms persist, usually less than a week.

Relationship to Other Conditions

Engraftment refers to newly transplanted cells taking root and producing in the bone marrow—that is, when they start the process of making new red blood cells, white blood cells, and platelets.

The relationship of engraftment syndrome to other post-transplant events that have similar features is controversial. These other post-transplant events include conditions such as acute GVHD, pre-engraftment syndrome, radiation- and drug-induced toxicities, and infections—alone or in combination.

Pre-engraftment syndrome and peri-engraftment syndrome are other terms that scientists have used to describe a similar set of symptoms that may arise around the time of engraftment.

Engraftment syndrome has also been called capillary leak syndrome, which refers to one of the possible underlying mechanisms of the syndrome. Due to the mix of cell signals and interactions found with engraftment syndrome, the body’s smallest blood vessels (capillaries) become more permeable than normal, resulting in abnormal, excess fluid building up in various parts of the body. When this occurs in the lungs, it is called noncardiogenic pulmonary edema.

A Word From Verywell

There is currently no consensus on the precise clinical definition of engraftment syndrome. However, given that this condition occurs after a serious medical procedure, your doctor will be monitoring your progress and will be in the best position to make a diagnosis, and prescribe treatment. Be sure to share any symptoms you may be experiencing with your treatment providers promptly.

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  1. Sheth V, Jain R, Gore A, Ghanekar A, Saikia T. Engraftment syndrome: clinical features and predictive factors in autologous stem cell transplant. Indian J Hematol Blood Transfus. 2018;34(3):448-453. doi:10.1007/s12288-017-0899-4

  2. Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27(9):893‐898. doi:10.1038/sj.bmt.1703015

  3. Chang L, Frame D, Braun T, et al. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomesBiol Blood Marrow Transplant. 2014;20(9):1407‐1417. doi:10.1016/j.bbmt.2014.05.022

  4. Spitzer, TR. Engraftment syndrome: double-edged sword of hematopoietic cell transplants. Bone Marrow Transplant. 2015;50(4):469-75. doi:10.1038/bmt.2014.296

  5. Sakaguchi H, Matsumoto K, Yoshida N, et al. Dexamethasone palmitate for patients with engraftment syndrome is associated with favorable outcome for children with hematological malignancy. Bone Marrow Transplant. 2016;51(11):1540-1542. doi:10.1038/bmt.2016.178

  6. Lee Y-H, Rah W-J. Pre-engraftment syndrome: clinical significance and pathophysiologyBlood Res. 2016;51(3):152-154. doi:10.5045/br.2016.51.3.152

  7. Clark SB, Soos MP. Noncardiogenic pulmonary edema. Treasure Island (FL): StatPearls Publishing; 2020 Jan.