Intervention: Methylprednisolone
Trial phase: Phase 2
ATC code: D07AA01 | D07CA02 | D10AA02 | H02AB04 | H02BX01 | S01CA08 | S03CA07
SMILES: [H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)C=C[C@@]21C
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 28
Group description: Patients receive etanercept IV (dose 0.4 mg/kg- max 25 mg) over 30 minutes on day 0 and subcutaneously (dose 0.4 mg/kg- max 25 mg) on days 3, 7, 10, 14, 17, 21, and 24. Treatment continues in the absence of an infectious pathogen, disease progression, or unacceptable toxicity. Patients also receive methylprednisolone (or corticosteroid equivalent) IV (dose 2.0 mg/kg/day) on days 0-2 and then orally with a taper beginning day 7. Dose on days 7-20 (1.0 mg/kg/day), days 21-34 (0.5 mg/kg/day), days 35-48 (0.25 mg/kg/day) and days 49-56 (0.25 mg/kg/every other day) discontinuing on day 56.

etanercept: Given IV and subcutaneously

methylprednisolone: Given IV and orally
Eligibility criteria:
Inclusion Criteria:

Diagnosis of acute, noninfectious idiopathic pulmonary dysfunction (IPS) as defined by the following:

Evidence of diffuse lung injury occurring within the first several months after hematopoietic stem cell transplantation for which an infectious etiology is not identified. To meet the criteria for IPS there must be:

Evidence of widespread alveolar injury

Diffuse multi-lobar infiltrates on chest x-ray or CT scan

Evidence for abnormal respiratory physiology based upon 1 of the following:

Room air oxygen saturation < 93%
Supplemental oxygen required to maintain an oxygen saturation ≥ 93%

Absence of active lower respiratory tract infection, defined as Bronchoalveolar lavage (BAL)-negative for infection based on one of the following:

Gram stain, fungal stain, acid-fast bacilli stain
Bacterial culture (a quantitative culture ≥ 10^4 colony-forming units/mL is considered positive)
Fungal culture
Mycobacterial culture

Viral culture (respiratory syncytial virus [RSV], parainfluenza, adenovirus, influenza A and B, and cytomegalovirus [CMV])

If direct fluorescent antibody (DFA) screening is performed on BAL, it must be negative for all viruses listed above
Pneumocystis carinii pneumonia by polymerase chain reaction (PCR), DFA stain, or cytology
Evidence of bilateral pulmonary infiltrates (on chest radiograph)
Patients may have diffuse alveolar hemorrhage (DAH) or peri-engraftment respiratory distress syndrome (PERDS)
Presence of "mixed oral flora," "rare Candida species," or the presence of a Penicillium species reported on BAL fluid analysis allowed
A radiographic finding of pulmonary edema does not exclude the diagnosis of IPS, provided the other criteria have been met and provided the treating physician concludes by clinical (or echocardiographic) criteria that the pulmonary edema is not secondary to cardiac dysfunction or iatrogenic fluid overload
Patients must require supplemental oxygen

Must have undergone an allogeneic bone marrow, cord blood, or peripheral blood stem cell transplantation within the past 120 days

There are no restrictions based upon underlying disease, donor source, the degree of HLA match, the intensity of the pre-transplant conditioning regimen, or the use of a prior donor leukocyte infusion
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

No documented invasive fungal or systemic viral infection within the past 14 days

Patients with asymptomatic viruria allowed
No signs of CMV reactivation (by CMV, PCR, antigenemia, or shell vial culture) within the past 14 days
No sepsis syndrome or hypotension that requires inotropic support (except dopamine < 5mcg/kg/minute)

No documented bacteremia within the past 48 hours

Persistent fever allowed
No evidence of cardiac failure by clinical or echocardiographic findings
No known hypersensitivity to etanercept
No known history of tuberculosis (Tb) or prior Tb exposure
No prior chronic hepatitis B or hepatitis C infection
Concurrent treatment for acute or chronic GVHD allowed
More than 14 days since prior etanercept
More than 7 days since prior investigational drug trials (phase I, II, or III) for the treatment of acute graft-versus-host disease (GVHD)
Not on mechanical ventilation for > 48 continuous hours prior to study entry
Must not be receiving > 2 mg/kg/day of methylprednisolone or corticosteroid equivalent within 24 hours of study entry
Concurrent continuous veno-venous hemofiltration or hemodialysis allowed