Diffuse Alveolar Hemorrhage and Infection-Associated Alveolar Hemorrhage following Hematopoietic Stem Cell Transplantation: Related and High-Risk Clinical Syndromes

Abstract

Diffuse alveolar hemorrhage (DAH) is a noninfectious pulmonary complication of hematopoietic stem cell transplantation (HSCT) with unclear pathogenesis and treatment. We reviewed prospectively collected data on 1919 consecutive transplants performed between 1995 and 2004 and compared patients with DAH and infection-associated alveolar hemorrhage (IAH) who presented with similar symptoms of hypoxemia, pulmonary infiltrates, and progressively bloody alveolar lavage but also had microorganisms isolated from blood, bronchoalveolar lavage, or tracheal aspirate within 1 week of alveolar hemorrhage. Overall, 116 patients had alveolar hemorrhage (45 with DAH, 71 with IAH). Older age, allogeneic donor source, myeloablative conditioning regimen, and acute severe graft-versus-host disease (GVHD) were independently predictive of an increased risk of post-HSCT alveolar hemorrhage. The DAH and IAH groups were comparable except for a higher proportion of patients receiving umbilical cord blood as a donor source and total-body irradiation-containing conditioning in the IAH group. The probability of 60-day survival from onset of hemorrhage was 16% (95% CI, 6%-26%) for the DAH and 32% (95% CI, 21%-43%) for the IAH group (P = .08). All except 20 patients were treated with a standard regimen of high-dose corticosteroids. Patients who received corticosteroids had 60-day survival of 26% (95% CI, 18%-34%), compared with 25% (95% CI, 6%-44%) for those who did not (P = .28). The pathogenesis of alveolar hemorrhage after HSCT is multifactorial, and we propose that IAH and DAH in HSCT recipients are related clinical syndromes with similar clinical presentation, risks, and associated high mortality.

Fatal diffuse alveolar hemorrhage associated with sirolimus after allogeneic hematopoietic cell transplantation

“…4 Myeloablative conditioning and severe acute GVHD are independent risk factors for alloHCT DAH. 4 The median time post-alloHCT to the onset of DAH was lesser in an earlier report 4 (28 days, range 3-280) when compared with the corresponding values for the three patients in our case series (3.3, 5.1 and 0.4 years, respectively, post-alloHCT).…”

“…4 Clinical suspicion of DAH and lung injury is usually confirmed by lung biopsy or autopsy. BAL will help exclude infectious etiologies.…”

“…SRL is widely used in SOT and recently in alloHCT. 2,4 We recommend that SRL toxicity be considered in the differential diagnosis when pulmonary symptoms are manifested as DAH/hypoxia and lung infiltrates in alloHCT patients receiving SRL.…”

Diffuse alveolar hemorrhage after unrelated cord blood transplantation

“…DAH after HSCT is reported in 1-5% of autologous graft recipients and in 3-7% of allogeneic graft recipients. [1][2][3][4] Umbilical cord blood transplantation (CBT) from unrelated donors has recently increased in popularity for adult patients with hematological diseases who have no other suitable donor. However, DAH in the setting of post CBT has not been discussed in detail.…”

“…However, DAH in the setting of post CBT has not been discussed in detail. 4 We describe herein, a case of a patient with DAH after CBT who was successfully treated with relatively low-dose steroid therapy using prednisolone at 1 mg/kg/day.…”