Cause of Death Options

Review the following guidelines when reporting the primary and contributing cause of deaths.

!Sepsis and Septic Shock
Sepsis and septic shock should not be reported as Other cause, as the true cause of death is an infection. Review the infection section below for additional details.

!Post-Transplant Lymphoproliferative Disorder (PTLD)
If PTLD is listed as a cause of death, report the cause of death as a New malignancy (post-infusion).

Recurrence / persistence / progression of disease for which the infusion was performed

• The cause of death is due to the primary disease for infusion, select Recurrence / persistence / progression of disease for which the infusion was performed
• If the cause of death is due to disease, ensure disease detected is reported on the appropriate post-infusion follow-up form.
• If the disease is present at death, but is not the underlying cause of death, this should be reported as a contributing cause of death.
  • Example: The recipient’s disease had been stable for months and they died by accidental means; this option should be used as a contributing cause of death (not the primary cause of death).

GVHD

• The determination of acute versus chronic GVHD should rest on clinical features identified by the clinician.
• Acute GVHD: If this is reported as a primary or contributing cause of death, acute GVHD should also be reported on the appropriate post-infusion form.
• Chronic GVHD: If this is reported as a primary or contributing cause of death, chronic GVHD should also be reported on the appropriate post-infusion form.
  

Graft failure or poor graft function

• Graft failure or poor graft function*: The recipient had no hematopoietic recovery, graft failure following initial hematopoietic recovery, or poor graft function.
• If secondary graft failure is due to GVHD or infection, also report GVHD or infection as causes of death.
  

Failure to thrive

• Failure to thrive is a term used to describe a global decline which includes inactivity, weight loss, and decreased appetite.
• Only applicable to report as a contributing cause of death
  

Hemorrhage

• Recipient died with evidence of hemorrhage.
• Use the following options to report the hemorrhage location: Diffuse alveolar hemorrhage (DAH), Gastrointestinal hemorrhage, Hemorrhagic cystitis, Intracranial hemorrhage, Pulmonary hemorrhage, or Other hemorrhage.
• Additional details:
  • Diffuse alveolar hemorrhage (DAH): If this is reported as the primary or contributing cause of death and the recipient is on the CRF track, also report this on the Post-Infusion Follow-Up (2100) Form.
  • Hemorrhagic cystitis: If this is reported as the primary or contributing cause of death and the recipient is on the CRF track, also report this on the Post-Infusion Follow-Up (2100) Form.
  • Intracranial hemorrhage: Also known as hemorrhagic stroke. If this is reported as the primary or contributing cause of death and the recipient is on the CRF track, also report this on the Post-Infusion Follow-Up (2100) Form.
  • Pulmonary hemorrhage: If this is reported as the primary or contributing cause of death and the recipient is on the CRF track, also report this on the Post-Infusion Follow-Up (2100) Form.
  • Other hemorrhage: Select this option if the hemorrhage was in an organ system that does not have a cause of death option and report the organ or location of the hemorrhage in the Specify data field.

Infection

• Recipient died due to an infection.
• Use the following options to specify the infection etiology: Bacterial infection, Fungal infection, Protozoal infection, Viral infection, or Other infection.
• If the organism was not identified, but evidence of infection was present based on clinical opinion, select Infection, organism not identified. Also report infections in the “Infection” section on the Post-Infusion Follow-Up (2100) or Cellular Therapy Essential Data Follow-Up (4100) Form.
• Additional details:
  • COVID-19: If the primary or contributing cause of death is COVID-19, select Viral infection.
  • Interstitial pneumonitis (IPn): Do not report IPn as an infection cause of death. Report IPn as Other pulmonary syndrome.
  • Pneumonia: If the primary or contributing cause of death is ‘pneumonia,’ report the cause of death as an infection (specify the etiology) or a pulmonary syndrome (specify the syndrome), if applicable. If the only details of the cause of death is ‘pneumonia’ (i.e., the infection etiology and / or pulmonary syndrome is unknown), select Infection, organism not identified.
  • Sepsis / septic shock
    • If the primary cause of death is ‘sepsis or septic shock,’ report the primary cause of death as an infection (specify the etiology) and the contributing cause of death as Multiple organ failure. If the infection etiology is unknown, select Infection, organism not identified.
    • If the contributing cause of death is ‘sepsis or septic shock,’ report the appropriate primary cause of death and specify the contributing cause of death as Infection (specify the etiology) and Multiple organ failure. If the infection etiology is unknown, select Infection, organism not identified.

Malignancy

• Recipient died with evidence of a malignancy other than the primary disease for infusion. Use the options below to specify the type of malignancy.
• New malignancy: If the recipient developed a new malignancy post-infusion, including PTLD, this should also be reported on the appropriate post-infusion form.
• Prior malignancy: If there was a history of malignancy prior to infusion (i.e., not the primary disease for infusion) and the recipient died with evidence of recurrence, persistence, or progression of the previous malignancy. This should also be reported on the appropriate pre-infusion form.
  

Organ failure (not due to GVHD or infection)

• Recipient died with organ failure, not due to GVHD or infection. Use the options below to specify the organ system that failed.
• Cardiac failure: If cardiac failure was related to congestive heart failure and / or myocardial infarctions, also report this on the appropriate Post-Infusion Follow-Up (2100) Form.
• Central nervous system (CNS) failure: Includes radiation-induced atrophy, brain stem dysfunction, or encephalitis of unknown origin.
  • Do not use this option if the cause of death is a brain infection (i.e., meningitis) – use the infection option.
  • Do not use this option if the cause of death is a hemorrhagic stroke – use Intracranial hemorrhage.
• Gastrointestinal (GI) failure (not liver): Includes intestinal obstruction or perforation.
  • Do not use this option if the cause of death is a GI hemorrhage – use Gastrointestinal hemorrhage.
  • Do not use this option if the cause of death is liver failure – use Liver failure (not VOD).
  • Do not use this option if the cause of death is GI GVHD – use Acute GVHD or Chronic GVHD.
• Liver failure (not VOD): Excludes veno-occlusive disease/sinusoidal obstruction syndrome (use VOD/SOS) and GVHD (use Acute GVHD or Chronic GVHD). If this is reported as the primary or contributing cause of death, also report this on the appropriate Post-Infusion Follow-Up (2100) Form.
• Multiple organ failure: If the cause of death is due to failure of more than one organ, provide additional detail and specify in question. Do not select this option if there is a root cause of the multiple organ failure (i.e., infection).
• Pulmonary failure: Includes pulmonary failure from non-infectious causes such as bronchiolitis obliterans (BO) or cryptogenic organizing pneumonia (COP). BO and COP should also be reported on the appropriate Post-Infusion Follow-Up (2100) Form.
• Renal failure: Renal failure that was severe enough to warrant dialysis (or the recommendation of dialysis) should also be reported on the appropriate Post-Infusion Follow-Up (2100) Form.
• Veno-occlusive disease (VOD) / sinusoidal obstruction syndrome (SOS): Include pulmonary veno-occlusive disease. Do not report other types of liver failure using this option. Liver VOD / SOS should also be reported on the appropriate post-infusion form.
• Other organ failure: If the organ system that failed is not specified, but present at death based on clinical opinion. Specify the organ involved.
  

Pulmonary

• Acute respiratory distress syndrome (ARDS) (other than IPS): Also known as adult respiratory distress syndrome. Acute onset, infiltrative respiratory distress. Excludes IPS. ARDS should also be reported on the appropriate Post-Infusion Follow-Up (2100) Form.
• Diffuse alveolar damage (without hemorrhage): Describes histologic changes found in lung disease. This is associated with ARDS and transfusion related acute lung injury (TRALI).
• Idiopathic pneumonia syndrome (IPS): Describes non-infectious lung injuries that occur post-infusion (within 100 – 120 days). IPS should also be reported on the appropriate Post-Infusion Follow-Up (2100) Form.
• Pneumonitis due to Cytomegalovirus (CMV): Pneumonitis can result from infection by cytomegalovirus, adenovirus, respiratory syncytial virus, influenza, or Pneumocystis jirovecii (PCP). Select this option if interstitial pneumonitis resulted from cytomegalovirus. Also report interstitial pneumonitis on the appropriate Post-Infusion Follow-Up (2100) Form.
• Pneumonitis due to other virus: Pneumonitis can also result from infection by adenovirus, respiratory syncytial virus, influenza, or Pneumocystis jirovecii (PCP). Select this option if pneumonitis was caused by a virus (other than CMV). Also report interstitial pneumonitis on the appropriate Post-Infusion Follow-Up (2100) Form
• Other pulmonary syndrome (excluding pulmonary hemorrhage): Select this option to report any other pulmonary syndrome, excluding pulmonary hemorrhage and specify the syndrome. Additionally, select this option for pneumonitis due to any other organism, specify IPn and the organism. Report interstitial pneumonitis on the appropriate Post-Infusion Follow-Up (2100) Form.
• Additional information:
  • If the primary or contributing cause of death is ‘pneumonia,’ report the cause of death as an infection (specify the etiology) or a pulmonary syndrome (specify the syndrome), if applicable. Refer to infection section above for more details.

Toxicity

• Cytokine release syndrome (CRS): Development of constellation of signs and symptoms seen post-infusion of monoclonal antibodies or cellular therapy products.
• Macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH) – like toxicities: Severe systematic inflammatory syndromes caused by excessive activation and expansion of T lymphocytes and macrophagic histocytes.
• Neurotoxicity (ICANS): The development of different neurologic signs and symptoms reported after the infusion of genetically modified lymphocytes.
• Tumor lysis syndrome: Disorder characterized by metabolic abnormalities resulting from spontaneous or therapy-related cytolysis of tumor cells.
  

Vascular

• Disseminated intravascular coagulation (DIC): Results in abnormal blood clotting.
• Ischemic stroke: Blood clot in an artery to the brain, preventing blood flow.
• Thromboembolism: Includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Report DVT or PE on the appropriate Post-Infusion Follow-Up (2100) Form.
• Thrombotic microangiopathy (TMA) (Thrombotic thrombocytopenia purpura (TTP) / Hemolytic Uremic Syndrome (HUS): A multifactorial condition where intravascular platelet activation, formation of thrombi, and microangiopathic hemolytic anemia occur due to generalized endothelial dysfunction. Report TMA or a similar syndrome on the appropriate Post-Infusion Follow-Up (2100) Form.
• Other vascular: Select this option to report any other vascular syndrome and specify.
  

Other

• Accidental death: Recipient death resulted from accidental or unintentional means.
• Suicide: Recipient intentionally caused their own death. In states where physician-assisted suicide is used to hasten death in terminally ill recipients, the cause of death should be reported as the underlying condition (primary cause of death) and suicide as a contributing cause of death.
• Stroke, unspecified: Recipient death was due to a stroke but the type of stroke is unknown.
• Other cause: If the cause of death is not listed above, select Other cause and specify. Do not include sepsis / septic shock or pneumonia.
  

Section Updates

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