Noninfectious complications of hematopoietic cell transplantation

Abstract

Noninfectious lung diseases contribute to nonrelapse mortality. They constitute a spectrum of diseases that can affect the parenchyma, airways, or vascular pulmonary components and specifically exclude cardiac and renal causes. The differential diagnoses of these entities differ as a function of time after hematopoietic cell transplantation. Specific diagnosis, prognosis, and optimal treatment remain challenging, although progress has been made in recent decades.

Graphical abstract

Figure 1.

Illustrated HCT noninfectious lung complications in terms of structure and peak timing after HCT. The time after HCT is shown on the x-axis (in months) with the diseases. Light blue bubbles, parenchymal processes (CRS; PERDS; CLS, capillary leak syndrome from endothelial damage; AIP; rP; DPTS; RLD). Red vessels, the endothelial processes (DAH; PVOD; PCT; TA-TMA). Green airway, airway disease (BOS). IPS, which is most often defined early post HCT, includes these diagnoses (defined by hypoxia, infiltrates, alveolar injury, and excludes later diagnoses that often do not present with these features). White box, pulmonary noninfectious diagnoses not specific to HCT (TRALI; TACO; COP; PE; PTLD), which can occur throughout the HCT trajectory. Above the table are key events occurring during HCT aGVHD and cGVHD.

Figure 2.

Flow diagram for workup and diagnosis of noninfectious lung diseases after HCT. Blue box, diseases commonly diagnosed in the first 100 days after HCT. Gray box, those diseases occurring usually beyond day 100 after HCT. Noninfectious lung injury workup and diagnoses are in boxes. *Additional pulmonary diagnoses are denoted by stars and listed in the column in which these diagnoses would be included in the differential. Notably, other processes can exhibit low DLCO, which is often reduced in RLD, but isolated DLCO reduction should prompt evaluation for vascular diseases of the lung. For the workup of obstructive disease, infection is often diagnosed, which should prompt repeat testing after treatment to ascertain BOS diagnosis (arrows). bx, biopsy; DLCO, diffusion capacity of lung for carbon monoxide; ID, infectious disease workup; PE, pulmonary embolism; toxin-IP, toxin associated interstitial pneumonitis, including that from radiation or chemotherapy.