Engraftment Syndrome Overview

Causes, Diagnosis, and Treatment

Stem cells


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

Engraftment is 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, however, it has been known to occur after both main types of HSCT: autologous (transplant from self) and allogeneic (from another, often related donor).

Engraftment syndrome symptoms may mimic those of graft versus host disease (GVHD), where donated bone marrow or stem cells react to the recipient's body as a foreign invader, triggering an immune response that attacks the body.

Symptoms and Diagnosis

Common symptoms exist along with less common, but whether or not they constitute an official diagnosis depends on specific criteria.

In 2001, Thomas R. Spitzer, MD, a clinical researcher at the Bone Marrow Transplant Program at Massachusetts General Hospital in Boston, MA, published the seminal paper on engraftment syndrome and his criteria have been used since to establish a diagnosis.

Major criteria:

  • Temperature greater than or equal to 100.9°F (38.3 °C) with no identifiable infectious cause
  • Red rash involving more than 25 percent of body surface area and not attributable to an infection or medication
  • Rash or 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)
  • Diarrhea without another cause

Minor criteria:

  • Liver dysfunction with certain parameters (bilirubin greater than or equal to 2 mg/dL or 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 percent of pre-transplant body weight)
  • Temporary confusion/brain abnormalities unexplainable by other causes

Diagnosis requires all three major criteria or two major criteria and one or more minor criterion within 96 hours (four days) of engraftment.

Symptoms are usually mild, but they can range to more severe and life-threatening forms.

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.

An important note on diagnosis: While Spitzer's criteria have been widely used to diagnose engraftment syndrome (and he published a follow-up in 2015), another researcher, Maiolino, established slightly different diagnostic criteria in 2004. While they also show fever, rash, pulmonary edema, and diarrhea, the specifics differ enough to have sparked debate.

That said, diagnosis will generally be achieved from these collective criteria.


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

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

Researchers reason that because engraftment syndrome is seen after 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, it is likely mediated by activated white blood cells and proinflammatory cell signals.

This mix of cell signals and interactions can cause a leaky circulatory system, organ dysfunction, and symptoms such as fever.


In many cases, engraftment syndrome may resolve on its own and require no treatment. A doctor must make this determination.

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

Relationship to Other Conditions

Engraftment refers to the newly transplanted cells “taking root and producing” in the bone marrow. That is, when they and 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 graft versus host disease (GVHD), pre-engraftment syndrome (PES), 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—that is, due to cell signals that are out of balance, the body’s smallest blood vessels, the 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 pulmonary edema. More specifically, it is fluid in the lungs not due to a heart problem, so the term is “noncardiogenic pulmonary edema.”

A Word From Verywell

How common is this syndrome, and what are the chances a particular patient will develop symptoms? Well, since there is no consensus on the precise clinical definition, wide ranges of incidences have been reported in the literature, from as low as 7 percent to as high as 90 percent in autotransplants (transplant from self as donor).

Given the circumstances of this condition, occurring after a serious medical procedure, your doctor will be monitoring your progress and be in the best position to identify symptoms, make the diagnosis, and prescribe any treatment.

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Article Sources

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  1. Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27(9):893-8. doi:10.1038/sj.bmt.1703015

  2. 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

  3. Maiolino, A., Biasoli, I., Lima, J. et al. Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteriaBone Marrow Transplant 31, 393–397 (2003). doi:10.1038/sj.bmt.1703855

  4. 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

  5. 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

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