Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection

Gad Allah Ali; Majed Altareb; Naeem Chaudhri; Feras Abdulaziz Alfraih

doi:10.4103/joah.joah_10_21

CASE REPORT

Year : 2023 | Volume : 14 | Issue : 1 | Page : 52-56

Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection

Gad Allah Ali¹, Majed Altareb², Naeem Chaudhri³, Feras Abdulaziz Alfraih⁴
¹ Hematology Fellow, Adult Hematology and Stem Cell Transplant, King Faisal Specialist Hospital and Research Centre, Oncology Centre, Riyadh, KSA
² Assistant Consultant, Adult Hematology and Stem Cell Transplant, Oncology Centre (MBC-64), Riyadh, KSA
³ Consultant, Adult Hematology/HSCT, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
⁴ President, Saudi Society for Blood Disorders, Director, Alternate Donor Stem Cell Transplant, Attending Physician, Adult Hematology/HSCT, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Date of Submission	06-Feb-2021
Date of Decision	29-Jun-2021
Date of Acceptance	07-Oct-2021
Date of Web Publication	17-Feb-2023

Correspondence Address:
Dr. Gad Allah Ali
Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh
KSA

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/joah.joah_10_21

Abstract

The current coronavirus disease 2019 (COVID 19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. The full impact of the COVID 19 pandemic, caused by the SARS CoV 2, on the field of hematopoietic cell transplantation (HCT) is unknown.Here, we report a rare case of a 21-year-old male patient known to have chronic myeloid leukemia (CML) with progression to T-cell lymphoblastic lymphoma as extramedullary blast crisis of CML. The patient was treated by pediatric chemotherapy regimen then. He underwent haploidentical stem cell transplantation. Posttransplantation, on day +7, he developed SARS-CoV-2 after receiving stem cell graft from a donor who was diagnosed with SARS-CoV-2 on the day of stem cells harvesting. The case elaborates complications and outcome of a patient receiving stem cell transplant from a donor with SARS-CoV-2 infection.

Keywords: Chronic myeloid leukemia, coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, T-cell lymphoblastic lymphoma, the European Society of Blood and Marrow Transplantation

How to cite this article:
Ali GA, Altareb M, Chaudhri N, Alfraih FA. Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection. J Appl Hematol 2023;14:52-6

How to cite this URL:
Ali GA, Altareb M, Chaudhri N, Alfraih FA. Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with a Donor and Recipient Infected with SARS-CoV-2 Infection. J Appl Hematol [serial online] 2023 [cited 2023 Mar 24];14:52-6. Available from: https://www.jahjournal.org/text.asp?2023/14/1/52/369837

Introduction

Coronavirus disease 2019 (COVID-19) disease is an infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).^[1],[2],[3] This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019.^[4] The WHO classified COVID-19 a pandemic on March 11.^[5] Although elderly and people with comorbidities are the most affected by the severe manifestations of the disease, patients undergoing hematopoietic stem cell transplantation (HCT) are a group of patients with special immunocompromised situation and could have potentially devastating outcome if they infected with SARS-CoV-2.^[6],[7] Data emerging about cancer patients show that these patients have an increased risk of complications and intensive care unit (ICU) admissions.^[8],[9] Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications,^[10],[11] and their course with COVID-19 disease is expected to be complicated.^[12] The patient who is reported here developed SARS-CoV-2 post-HCT who received stem cells from donor diagnosed with SARS-CoV-2 by nasopharyngeal swab on the day of the HCT. It is possible that this might be one of the rarest cases during the pandemic.

Case Report

A 21-year-old male patient who was diagnosed as chronic myeloid leukemia (CML) presented with T-cell lymphoblastic lymphoma (T-cell LBL) as extramedullary blast crisis. He was treated with pediatric chemotherapy regimen (Children's Oncology Group protocol) plus imatinib in August 2019. Peripheral blood BCR/ABL p210 postinduction in October 2019 was 29%. Tyrosine kinase inhibitor (TKI) was changed to dasatinib. He achieved major molecular remission (MMR). He was referred for haploidentical stem cell transplant, as he did not have matched sibling donors. The patient was not known to have any other medical illness and no family history of hematological malignancies.

During pretransplant workup, the patient was found to have sickle cell trait; HbS: 30%. Bone marrow biopsy showed no evidence of T-LBL. BCR-ABL IS% was 0.01%, indicating complete remission with Minimal residual disease (MRD) + at MMR at >4.0 log reduction.

The patient was admitted on June 7, 2020, for haploidentical stem cell transplantation from bone marrow source from his father, an HLA-mismatched and ABO-matched donor. The patient and the donor were tested negative for SARS-CoV-2 on admission. Conditioning regimen consisted of Total body irradiation (TBI) 1000 cGy on day −10 to day −8, fludarabine 30 mg/m² on day −7 to day −4, and rabbit antithymocyte globulin 2 mg/kg on day −3 and day −2. All measures for COVID-19 prevention were followed as per local hospital policy. The donor (father) was admitted 1 day before bone marrow harvest procedure for stem cell collection. Nasopharyngeal swab for SARS-CoV-2 was done as routine workup according to the hospital policy. Swab result showed positive for SARS-CoV-2. Donor was asymptomatic. The decision was made to change the stem cell source from BM harvest procedure to peripheral blood stem cell (PBSC) collection to reduce the risk of exposure to operating room staff. Surveillance swab for the other members of the family revealed positive results for all members. All family members were restricted from visiting the patient.

PBSC collection was done in two sessions. All involved medical staffs wore enhanced personal protection equipment. Stem cells dose was 6.02 × 10⁶ CD34 cells/kg. This harvested PBSC was tested negative for SARS-CoV-2 by Reverse transcription-polymerase chain reaction (RT-PCR).

The donor was evaluated by hospital infectious disease team. He received hydroxychloroquine orally and was advised to continue home isolation for 14 days.

The patient stayed in airborne infection isolation unit after transplantation. His graft versus host disease (GvHD) prophylaxis consisted of posttransplant cyclophosphamide day +3 and day +5, cyclosporine from day +4, and mycophenolate mofetil from day +1. The infection prophylaxis medications were acyclovir and caspofungin.

Patient's nasopharyngeal swab for SARS-CoV-2 was negative on day −1 and day +5. On day +7, the patient tested positive by nasopharyngeal swab by SARS-CoV-2. He was labeled as mild COVID-19 infection and was advised to start treatment with azithromycin, hydroxychloroquine, and hydrocortisone. The patient was shifted to the ICU for close observation. He was afebrile with no respiratory symptoms. He received tocilizumab 400 mg intravenous (IV) on day +9 and +14 as his inflammatory markers showed high ferritin level at 3312 ug/L, interleukin-6 at 74.2 pg/ml, ESR 73 mm/h, procalcitonin 0.34 ng/ml, CRP 8.8 mg/L, LDH 180 U/L, and CK 21 U/L. He had negative blood cultures, CMV was 177 IU/ml, Aspergillus galactomannan was nonreactive, normal liver and renal functions were normal. Clinical status remained stable. The patient as expected remained with severe pancytopenia at this stage. Venous thromboembolism prophylaxis (VTE) prophylaxis was on hold because of thrombocytopenia; Granulocyte-colony stimulation factor (G-CSF) was suspended to prevent the risk of cytokines release storm. The patient was transferred back to the Bone marrow transplantation (BMT) unit isolation room on day +14. On day +18, he developed mild cough and shortness of breath, leading to readmission to ICU. The patient developed progressive COVID-19 pneumonia as chest CT scan showed interstitial infiltration pattern (bilateral ground glass opacities). He had further elevation in the inflammatory markers and serial readings of ferritin increased reaching as high as 83,057 ug/L (pretransplant ferritin 600 ug/L) on day +18 [Figure 1]. Interleukin-6 increased reaching as high as 273.9 pg/ml [Figure 2]. This was also associated with rise in liver enzymes [Figure 3]. It was all attributed to SARS-CoV-2, leading to macrophage activation syndrome as well as cytokine release syndrome (CRS). Accordingly, the patient was managed with dexamethasone (6 mg IV daily for 10 days), IV immunoglobulin 20 gm daily for 5 days, and ruxolitinib 5 mg orally BID. After the above treatment and addition of ruxolitinib, his inflammatory markers were resolved.

Figure 1: Ferritin level

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Figure 2: Interleukin-6 level

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Figure 3: Liver enzymes level

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The patient had no evidence of acute GvHD or veno-occlusive disease clinically or biochemically. Platelet engrafted on day +9, while neutrophils engrafted on day +23.

He recovered and remained asymptomatic with resolution of CT chest infiltration.

The patient was safely discharged home after 46 days of hospital stay. His serum ferritin level was 11,919 ug/L.

During clinic follow-up, his engraftment showed 100% donor chimerism. No acute GvHD features were noted. GvHD prophylaxis continued on cyclosporine (CSA) and also remained on ruxolitinib 5 mg BID. His repeated nasal SARS-CoV-2 PCR on day +72 was negative, and his SARS-CoV-2 total antibody test was not reactive which was expected in view of ongoing post-Allo-stem cell transplantation (Allo-SCT) immunosuppression.

Discussion

Hematological malignancies patients are particularly at risk of developing serious respiratory adverse events related to COVID-19.^[12],[13] At the same time, any inappropriate delay of a life-saving treatment such as allogeneic transplantation may be detrimental for their survival.

This clinical case describes a typical scenario of difficult clinical decision-making in the COVID-19 pandemic era. This young patient who had CML with T-cell LBL blast crisis in MMR postinduction with pediatric chemotherapy protocol and TKI required an HCT without delay. This patient tested positive for SARS-CoV-2 on day +7 of haplo-HCT. The donor tested positive for SARS-CoV-2 on the day of stem cell harvesting as well as many other family members. The harvested product was negative for SARS-CoV-2 by PCR technique. The patient nasopharyngeal swab for SARS-COV-2 was negative on day +1 and day +5 but converted to positive on day +7. We assume that he acquired the infection through transmission from his family members rather than from the apheresis product. In our report, stem cell harvest was also negative by PCR.

The guidelines developed by members of the American Society for Transplantation and Cellular Therapy Infectious Diseases Special Interest Group recommend that all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens before procedures and not more than 2–3 days before conditioning and lymphodepletion. Exposed patients should be closely monitored for the development of symptoms, and if none, they should have two consecutive negative PCR tests ≥24 h apart before proceeding with required procedures. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible to donate. However, an ineligible donor may be collected in certain situations with reference to the facility standard of practice for circumstances for use and documentation of urgent medical need and appropriate counseling on risks and benefits of HCT.^[14]

According to the European Society of Blood and Marrow Transplantation guidelines version 10 on September 15, 2020, all patients should be tested for SARS-CoV-2 by PCR and the test results should be negative before start of the conditioning regardless of whether any symptoms are present. In general, however, if a transplant candidate is diagnosed with COVID-19 a deferral of at least 3 months is advisable according to European Centre for Disease Prevention and Control recommendations. However, this is not always possible due to the risk for progression of the underlying disease. The decision must be made based on individual considerations taking into account the risk to the patient, any delay of the procedure, and the risk of proceeding with conditioning therapy. In case of diagnosis of COVID-19, donor must be excluded from donation. Collection should be deferred for at least 28 days after recovery. While the donor is completely well and there are no suitable alternative donors, an earlier collection may be considered if local public health requirements permit, subject to careful risk assessment. Risk assessment should be based on the date of full recovery, the duration and severity of COVID-19, and the results of postrecovery testing.^[15]

The course of our patient suggests that immunosuppressive patients are at high risk of developing complications of COVID-19 pneumonia and CRS. The patient was treated and supported as any other COVID-19 patient with complications, and the outcome was satisfactory recovery, stressing full supportive care for such patients. One factor in full recovery despite CRS and pneumonia was likely the young age of the patient. In general, the guidelines should be adhered to; however, in specific situations, HCT can be carried on with close evaluation and timely intervention for any complication as in this case.

Conclusions

During this COVID-19 pandemic era, any patient for whom an allogeneic transplant is planned should be tested with nasopharyngeal swab for SARS-CoV-2 infection, especially before hospital admission. If the result for SARS-CoV-2 infection proves negative, the transplant procedure should be pursued as planned. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible to donate. However, an ineligible donor may be collected in certain situations where delay is not possible or unavoidable.

Posttransplant care in HCT recipients with COVID-19 infection is feasible in regular transplant units, provided the patient does not present with respiratory symptoms or failure. Early and repeated testing for SARS-CoV-2 in posttransplant patients with concomitant infection mitigation strategies should be considered in patients who develop fever, respiratory symptoms, and/or gastrointestinal symptoms to control the spread of COVID-19 both in patients and healthcare workers in hospital environments.

Clinical decision-making and team work are crucial for patient survival in the COVID-19 pandemic era.

In this case of an asymptomatic SARS-CoV-2–positive recipient, stem cell transplantation was pursued as planned from an asymptomatic SARS-CoV-2–positive stem cell donor with no significant adverse CRS or infection-related outcome in the recipient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Algwaiz G, Aljurf M, Koh M, Horowitz MM, Ljungman P, Weisdorf D, et al. Real-world issues and potential solutions in hematopoietic cell transplantation during the COVID-19 pandemic: Perspectives from the Worldwide Network for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research Health Services and International Studies Committee. Biol Blood Marrow Transplant 2020;26:2181-9.
2.	Ardura M, Hartley D, Dandoy C, Lehmann L, Jaglowski S, Auletta JJ, et al. Addressing the impact of the coronavirus disease 2019 (COVID-19) pandemic on hematopoietic cell transplantation: Learning networks as a means for sharing best practices. Biol Blood Marrow Transplant 2020;26:e147-60.
3.	Ortiz-Prado E, Simbaña-Rivera K, Gómez-Barreno L, Rubio-Neira M, Guaman LP, Kyriakidis NC, et al. Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the coronavirus disease 2019 (COVID-19), a comprehensive literature review. Diagn Microbiol Infect Dis 2020;98:115094.
4.	Cheng VC, Wong SC, Chen JH, Yip CC, Chuang VW, Tsang OT, et al. Escalating infection control response to the rapidly evolving epidemiology of the coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infect Control Hosp Epidemiol 2020;41:493-8.
5.	Ljungman P, Mikulska M, de la Camara R, Basak GW, Chabannon C, Corbacioglu S, et al. The challenge of COVID-19 and hematopoietic cell transplantation; EBMT recommendations for management of hematopoietic cell transplant recipients, their donors, and patients undergoing CAR T-cell therapy. Bone Marrow Transplant 2020;55:2071-6.
6.	Adam A. COVID? 19 post hematopoietic cell transplant, a report of 11 cases from a single center. Mediterr J Hematol Infect Dis 2020;12:e2020070.
7.	Martins-Chaves RR, Gomes CC, Gomez RS. Immunocompromised patients and coronavirus disease 2019: A review and recommendations for dental health care. Braz Oral Res 2020;34:e048.
8.	Anurathapan U, Apiwattanakul N, Pakakasama S, Pongphitcha P, Thitithanyanont A, Pasomsub E, et al. Hematopoietic stem cell transplantation from an infected SARS-CoV2 donor sibling. Bone Marrow Transplant 2020;55:2359-60.
9.	Fung M, Babik JM. COVID-19 in immunocompromised hosts: What We know so far. Clin Infect Dis 2021;72:340-50.
10.	Eichenberger EM, Soave R, Zappetti D, Small CB, Shore T, van Besien K, et al. Incidence, significance, and persistence of human coronavirus infection in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2019;54:1058-66.
11.	Waghmare A, Englund JA, Boeckh M. How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation. Blood 2016;127:2682-92.
12.	Fox TA, Troy-Barnes E, Kirkwood AA, Chan WY, Day JW, Chavda SJ, et al. Clinical outcomes and risk factors for severe COVID-19 in patients with haematological disorders receiving chemo- or immunotherapy. Br J Haematol 2020;191:194-206.
13.	Al-Shamsi HO, Alhazzani W, Alhuraiji A, Coomes EA, Chemaly RF, Almuhanna M, et al. A practical approach to the management of cancer patients during the novel coronavirus disease 2019 (COVID-19) pandemic: An International Collaborative Group. Oncologist 2020;25:e936-45.
14.	Waghmare A, Abidi MZ, Boeckh M, Chemaly RF, Dadwal S, El Boghdadly Z, et al. Guidelines for COVID-19 management in hematopoietic cell transplantation and cellular therapy recipients. Biol Blood Marrow Transplant 2020;26:1983-94.
15.	Ljungman P. Coronavirus disease covid-19: EBMT recommendations. Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA: The European Society for Blood and Marrow Transplantation; 2020. p. 2020-06.