Frequency, Clinical Characteristics and Outcome of Adult Patients with Acute Lymphoblastic Leukemia (ALL) and COVID-19 in Spain: Results of a Survey from Pethema and Geth Groups
Authors: Ribera Josep-Maria , Morgades Mireia , Coll Rosa , Lopez Lorenzo Jose Luis , Montesinos Pau , Varela Rosario , Cabrero Mónica , Gómez-Centurión Ignacio , Morales M. Dolores , Garcia-Guiñon Antoni , Bautista Guiomar , Herrera Puente Pilar , Llorente Laura , García-Cadenas Irene , Barba Pere , Calbacho Maria , Gil Cristina , Foncillas Maria Angeles , Artola María Teresa , De La Camara Rafael , Piñana Sanchez Jose Luis 
Published: November 2020

Introduction and objective. SARS-CoV-2 pandemic has deeply impacted in Spain. In cancer patients (pts) the lethality has been higher than in normal population, but, little is known on the impact in adults with ALL. Our objective was to analyze the frequency, clinical characteristics and outcome of adult ALL patients infected by SARS-CoV-2.
Methods. Between March 1, 2020 and May 31, 2020 (the period of the peak of COVID-19 infection in Spain) two registries from the PETHEMA (Programa Español de Tratamientos en Hematologia) and GETH (Grupo Español de Trasplante Hematopoyético y Terapia Celular) groups were activated to recruit adult patients with ALL and COVID-19 infection confirmed by PCR. The PETHEMA registry was based on ASH proposal (www.ashresearchcollaborative.org/covid-19-registry) and the GETH registry was specifically performed for hematological diseases and COVID-19 infection. Both registries were merged for this study. Eighty-four Spanish centers were contacted and weekly reminds were sent until May 19, 2020. The demographic and clinical characteristics of ALL and COVID-19 infection, the comorbidities, the treatment and outcome were collected. The study was closed for follow in July 10, 2020.
Results. Fifty-six of 84 centers answered the survey and 28 patients with ALL and COVID-19 infection were identified in 17 of them, especially on March (n=11) and April (n=15). Median age was 46 (range 20-78) yrs. and 19 were aged over 40 yrs. Fifteen pts were male, 1 was active smoker and 9 showed one or more comorbidities (chronic liver disease [n=2] diabetes [n=1], hypertension [n=5], cardiopathy [n=2], prior malignancy [n=1] and hypogammaglobulinemia [n=1]). ALL was of B-cell precursors in 18 pts (Ph+ in 6) and T in 10. Twenty-six pts were on treatment of LAL (induction [n=10], consolidation [n=3], maintenance [n=1], HSCT [n=5], rescue [n=6], and palliative [n=1]). Eight patients were previously submitted to allogeneic HSCT, CAR T [n=1] or immunotherapy with monoclonal antibodies (inotuzumab, n=4) and 21 were receiving immunosuppressive drugs (corticosteroids in 11, fludarabine in 4, among others). Eleven pts showed neutropenia &lt;0.5x109/L and 18 lymphocytopenia &lt;0.5x109/L. Median value of C reactive protein was 28.7 mg/L (0.9-311.7) and D-dimer 690 ng/mL (120-31,200). The main clinical characteristics of COVID-19 infection were: fever (n=18), cough (n=16), shortness of breath (n=9) and asthenia (n=11) and 5 pts were asymptomatic. The most frequency therapies were hydroxychloroquine/chloroquine (n=23), combined or not with lopinavir/ritonavir. Tocilizumab was given to 8 pts. Twelve pts required oxygen supply and 7 required ICU support (median stay 16 [1-47] days). COVID-19 was solved in 18 pts, although 5 pts showed PCR+ persistence (median 25 [16-91] days) after resolution of symptoms. The treatment of ALL was stopped/modified in 11 pts. Nine pts dead (COVID-19 [n=6], COVID-19 and ALL progression [n=2] and COVID-19 andPseudomonassepsis [n=1]). A trend for higher mortality was observed in patients with neutropenia &lt;0.5x109/L and in those with lymphocytopenia &lt;0.5x109/L.
Conclusion. The frequency of adult patients with ALL and COVID-19 infection can be considered high, given the low incidence of adult ALL. COVID-19 infection was frequent in patients with advanced age and on ALL therapy. The frequency of severe COVID-19 infection and the mortality were high.
Supported in part by 2017 SGR288 (GRC) Generalitat de Catalunya and "la Caixa" Foundation.

Disclosures
Ribera: Pfizer, Amgen, Ariad, Novartis:Consultancy, Speakers Bureau;Pfizer, Amgen:Research Funding.Barba:Amgen, Celgene, Novartis, Pfizer:Speakers Bureau;Amgen, Celgene, Gilead, Jazz Pharmaceuticals, Novartis, Pfizer, Shire:Consultancy.