Hematologic patients have been reported to be among the most affected during the COVID-19 pandemic due to the immunosuppression they are receiving; the hematopoietic cell transplant (HCT) patients are the most affected. In this group, a higher morbimortality has been detected with mechanical ventilation rates of 14% and deaths of 33-35%. The most affected are the recipients of HCT in the last year and presented the highest risk of death.^1,2

The immunosuppression also alters the response to the SARS-CoV-2 vaccination because we now know that patients with hematological malignancies show neutralizing antibodies of 57-60% and cellular responses of 40-75% after two doses of an mRNA vaccine.³

Treatment against moderate to severe COVID-19 has focused on hindering the hyperimmune response generated by the virus with several tools, including the tyrosine kinase inhibitors baricitinib and ruxolitinib. However, phase II and III studies employing these drugs have included hematologic diseases and prior immunosuppression in their exclusion criteria.^4-6

A 65-year-old male diagnosed with Ph+ acute lymphoblastic leukemia was treated with HYPER-CVAD. He had persistence of positive minimal residual disease, so a haploidentical bone marrow transplantation (from his son) was performed.

Pre-transplant desensitization was performed with rituximab and intravenous immunoglobulin due to the presence of donor-specific anti-HLA antibodies. Conditioning was carried out based on 200 cGy total body irradiation, fludarabine, and cyclophosphamide; the reception of progenitor cells took place on February 9^th, 2021. Prophylaxis against graft-versus-host disease (GVHD) was given with a high-dose cyclophosphamide at day +3 and +4 and tacrolimus; mycophenolate mofetil from day +5.

Immediate post-transplant complications included left parotitis, obstructive uropathy (due to right ureteral lithiasis with BK virus viruria that caused acute kidney injury), hepatic GVHD (which required intravenous corticosteroid treatment), and pneumonia with bilateral pleural effusion (requiring thoracentesis in both hemithoraces).

At day +30, imaging suggestive of Pneumocystis jirovecii was detected, which resolved following trimethoprim/sulfamethoxazole (TMP/SMX) for 14 days. The patient presented myeloid graft at day +24 and platelet graft at day +29 with 100% chimerism. The patient had no eventualities during the following three months. He was receiving GVHD prophylaxis with tacrolimus 1 mg/day and bosutinib 100 mg every 12 hours as maintenance.

At five months, he showed signs of herpes zoster, which improved with acyclovir without any complications.

The patient was not vaccinated against COVID-19 because he was in the first six months post-transplant.

He went for medical evaluation on August 5^th, 2021 (day + 176 post-transplant) due to the presence of dry cough, fever, malaise, and diarrhea. On clinical examination, he had a pulse oximetry saturation of 85%.

Based on those findings, he was sent to the emergency room where a chest CT scan was performed. This study reported imaging changes suggesting atypical pneumonia, described as infiltrates resembling ground glass, most evident in the periphery of the upper lobes and middle lobe. Alveolar infiltrates were also observed in the lower lobes, associated with interstitial thickening, irregular reticular appearance, and centrilobular micronodular pattern.

Laboratory tests showed leukocytes 7,100 cells/mm³, bands 8%, neutrophils 53%, hemoglobin 11.2 g/dL, platelets 55,000 cells/mm³, C-reactive protein 13.62 mg/L, ferritin 3,531 ng/mL, D-dimer 2165 ng/mL, glucose 110 mg/dL, creatinine 1.35 mg/dL, lactate dehydrogenase 280 IU/L. A diagnosis of COVID-19 pneumonia was confirmed after positive PCR for SARS-CoV-2 on August 5^th, 2021.

Treatment was started with ruxolitinib 10 mg orally every 12 hours, rivaroxaban 20 mg orally every 24 hours, and prophylactic TMP/SMX because of a history of P. jirovecii.

On August 6^th, 2021, only a few hours after starting treatment and supplemental oxygen, the patient requested a transfer to a hospital in his city of origin because of insurance reasons.

Upon arrival, there was no hospital availability, so care was continued at home without oxygen supplementation, he maintained an oxygenation >90%. The patient completed fourteen days of treatment, showing favorable evolution at home, without requiring supplemental oxygen. At the end of treatment, he was asymptomatic and had no sequelae data of COVID-19.

Laboratory tests taken on August 23^rd 2021 showed leukocytes 5,600 cells/mm³, bands 0%, neutrophils 35%, lymphocytes 57%, hemoglobin 11. 2 g/dL, platelets 55,000 cells/mm³, C-reactive protein 28 mg/L, ferritin 2340 ng/mL, D-dimer 2067 ng/mL, alkaline phosphatase 187 UI/L, lactate dehydrogenase 270 UI/L, creatinine 1.6 mg/dL; the rest of the tests were unremarkable.

Imaging also showed a favorable evolution with a control study on August 10^th, 2021: chronic obstructive pneumopathy, multifocal ground-glass opacities, CoRADS 6, overdistended pulmonary parenchyma, diffuse alveolar infiltrates (with some linear atelectasis), angiosclerosis, spondylarthrosis, and lithiasis.

A second CT scan on August 23^rd reported fibrous adhesions in scarce ground glass foci, in relation to a recent infectious process, changes due to chronic pneumopathy, angiosclerosis, and right renal lithiasis (Photography 1).

Photography 1. Pulmonary changes under ruxolitinib treatment by pulmonary CT-scan. Chest-CT findings suggestive of atypical pneumonia with ground glass infiltrates periphery of the upper lobes and middle lobe with a control study on August 10^th and August 23^rd showing improvement of infiltrates

The patient is currently alive and in good general conditions, without oxygen requirement or sequelae of COVID-19; there are no data of treatment complications, post-transplant complications, or leukemia relapse.