INTRODUCTION
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) caused the current global pandemic of coronavirus disease 2019 (COVID‐19). Although most patients with COVID‐19 have mild symptoms, some have more severe manifestations. 1 Recent findings have suggested an association between cancer and an increased risk of developing severe symptoms of COVID‐19. 2 , 3 , 4 Dai et al. reported that about 39% of the COVID‐19 patients with cancer had severe events such as intensive care unit admission, the need for mechanical ventilation, and even death. They showed that only 8% of the COVID‐19 patients without cancer had those severe symptoms. 5 In addition, hematologic cancer patients with COVID‐19 had a high frequency of severe events like a higher mortality rate and a more severe COVID‐19 course. 6 The immune system dysfunction is one of the main reasons that confirm patients with hematological malignancies are more vulnerable. 7 Moreover, anti‐cancer therapies such as chemotherapy, radiotherapy, and immunosuppressive drugs worsen the condition of these patients. 8 There are a limited number of studies on the prevalence of comorbidities and mortality rate in COVID‐19 patients with hematological malignancies. Therefore, in this systematic review and meta‐analysis, we will comprehensively review the available published literatures reporting the COVID‐19 outcomes and underlying diseases in patients with hematological malignancies from around the world.
MATERIALS AND METHODS
This study was performed following the “Preferred Reporting Items for Systematic Reviews and Meta‐Analyses” (PRISMA) statements. 9
Search strategy
The Pubmed/Medline, Embase, and Web of Science databases, from January 1, 2019, until March 10, 2021, were searched to collect the potentially relevant articles reporting COVID‐19 disease in patients with hematological malignancies. The search was limited solely to publications in English.
The following keywords or Medical Subject Headings (MESH) terms were used in text, title, or abstract with the help of Boolean operators (“and,” “or”): “COVID‐19,” “severe acute respiratory syndrome coronavirus 2,” “SARS‐CoV‐2,” “nCoV disease,” “2019‐nCoV,” “coronavirus disease 2019,” “bone marrow cancer,” “blood cancer,” “myeloma,” “lymphoma,” “Waldenstrom macroglobulinemia,” “leukemia,” “hematological malignancy,” “myelodysplastic syndrome,” and “myeloproliferative disorder.”
Study selection
All the articles reporting COVID‐19 positive patients with at least one type of hematological malignancies were included. In other words, patients with blood cancer infected with the SARS‐CoV‐2 were enrolled in the study. The allogeneic stem cell transplantation patients were included as well. According to World Health Organization (WHO) guidelines, COVID‐19 cases are defined as patients whose reverse transcription‐polymerase chain reaction (RT‐PCR) is positive. Duplicate publications, narrative reviews, meta‐analyses, systematic reviews, editorials, correspondences, guidelines, articles published in languages other than English, and publications without enough data or available only in abstract form were also excluded. The included studies were screened in two stages for eligibility. First, title/abstract screening was done, and then, the full text of those that had the inclusion criteria was retrieved. It is worth noting that although we reviewed case‐report articles to evaluate some variables, only research articles and case series were included for meta‐analysis.
Data extraction
The extracted data included the first author’s name, country of the study, published time, type of study, number of patients, median age, gender, hematological malignancy type, blood cancer therapy, the median duration of blood cancer, COVID‐19 diagnosis method, COVID‐19 therapy, clinical manifestations, laboratory findings, comorbidities, and outcome. Two authors independently applied the inclusion criteria to the potentially relevant article, and discrepancies between the authors were resolved by consensus discussion.
Quality assessment
The quality assessment of the studies was carried out through the critical appraisal checklist provided by the Joanna Briggs Institute (JBI). 10
Meta‐analysis
Data were analyzed using STATA software, version 17.0. The fixed‐effects model and random‐effects model were used to compute pooled estimates of the relative risk. The heterogeneity was quantified by the Cochran Q statistic and I 2 statistical methods. The p ‐value <.05 was considered statistically significant. 11
RESULTS
Characteristics of included studies
Initially, a total of 1169 articles were collected from databases. After removing the duplicates, 704 studies remained. In the screening phase, 548 of them were excluded through the title and abstract evaluation. Out of these studies, 53 met the inclusion pellucid criteria based on the full‐text screening. At the final stage, 15 eligible articles were included in the meta‐analysis (Figure 1 ). Characteristics of the selected articles are summarized in Table 1 . Most of the studies took place in Spain (8/53, 14.81%), followed by the United States (6/53, 11.11%), China (5/53, 9.26%), and the United Kingdom (5/53, 9.26%).
TABLE 1
Characteristics of the included studies
| First author | Country | Publish time | Type of study | No. of patients with blood cancer & COVID‐19 | Median age | Male/female | Type of blood cancer | Treatment of blood cancer | Median duration of Blood cancer | SARS‐CoV‐2 diagnosis method | COVID‐19 treatment and ancillary medications | Clinical manifestations | Laboratory findings | Other comorbidities | Outcomes |
| Santana 33 | Brazil | Feb 2021 | Case report | 1 | 47 | F | Grade 3A follicular lymphoma | rituximab, cyclophosphamide, vincristine, and PRED | NR | RT‐PCR, CT scans | mPDRL, oxygen support | Dyspnea, hypoxemia | Increased: D‐dimer, CRP | organizing pneumonia | Discharged |
| Ali 34 | Qatar | Oct 2020 | Case report | 1 | 49 | M | CLL | None | NR | RT‐PCR, CT scans | OTV, AZ, HCQ, IV CRO, amoxicillin/clavulanate | Fever, mild dyspnea, body aches | Increased: WBC, ANC, lymphocyte, monocyte, ferritin, CRP Decreased: Albumin | None | Discharged |
| Nesr 35 | UK | Sep 2020 | Case report | 1 | 80 | F | CLL | NR | NR | RT‐PCR, CT scans | IV DOX, oxygen support | Fever, cough, dyspnea | Increased: Lymphocyte, reticulocyte, LDH, bilirubin, CRP Decreased: Hb | congestive cardiac failure, atrial fibrillation, AIHA | Discharged |
| Molina‐Cerrillo 36 | Spain | Jan 2021 | Case report | 1 | 72 | M | CLL | IBR | 4y | RT‐PCR, CT scans | Oxygen support, HCQ, LPV/r | Cough, sore throat, fever | Increased: D‐dimer, CRP, LDH, lymphocyte, ferritin, IL‐6, IL‐8 | Hypertension, dyslipidemia | Discharged |
| Largeaud 37 | France | Nov 2020 | Case report | 1 | 83 | M | CLL | NR | NR | RT‐PCR, CT scans | Paracetamol, amoxicillin, clavulanic acid, corticosteroid therapy, anticoagulant therapy, oxygen support | Fever, cough, dyspnea, rectal bleeding | Increased: CRP Decrease: Hb, WBC, ANC, lymphocyte, PLT | radiotherapy treated pulmonary neoplasia | Discharged |
| Bolaman 38 | Turkey | Feb 2021 | Case report | 1 | NR | F | DLBCL | Chemotherapy | NR | RT‐PCR, CT scans | HCQ, AZ, favipiravir, oxygen support | Cough, dyspnea, orthopnea | Increased: Fibrinogen, D‐dimer, LDH Decreased: Hb, WBC, lymphocyte | NR | Death |
| Pasin 39 | Africa | Jul 2020 | Case report | 1 | 20 | M | Refractory NK/T‐cell lymphoma | rituximab, pembrolizumab, l‐asparaginase | NR | RT‐PCR, CT scans | RBC transfusions, mPDRL, Oxygen support, IV levofloxacin, supportive therapy, steroid therapy | Fatigue, fever, cough, dyspnea | Increased: WBC, CRP, LDH, indirect bilirubin Decreased: Hb, PLT | EBV, AIHA | Discharged |
| Ibrahim 40 | Saudi Arabia | Sep 2020 | Case report | 1 | 57 | M | CML | Imatinib | 10y | RT‐PCR, CT scans | Paracetamol and antitussive‐ HCQ, AZ, CRO, enoxaparin, oxygen support, mPDRL, LPV/r, ribavirin, IFN | Cough, fever, nausea | Increased: WBC, ANC, lymphocyte, D‐dimer, ferritin, LDH | Diabetes mellitus | Discharged |
| Chaidos 41 | UK | May 2020 | Case series | 2 | 62.5 | M 2 | MM 2 | lenalidomide 1, bortezomib 1, panobinostat 1 | NR | RT‐PCR, CT scans | Tocilizumab 2, oxygen support 1 | Fever 2, cough 1, hypoxia 2 | Increased: CRP 2, ferritin 2, D‐dimer 2 | NR | Discharged 2 |
| O’Kelly 42 | Ireland | May 2020 | Case report | 1 | 22 | F | HL | ABVD, BEACOPP, ICE, brentuximab vedotin, IFRT, pembrolizumab | 4y | RT‐PCR, CT scans | TZP, DOX, LPV/r, antibiotics, HCQ, AZ, oxygen support, corticosteroids | Cough, fever, sore throat, chills, rigors | Increased: CRP, LDH Decreased: Lymphocyte, PLT | NR | Discharge |
| Day 43 | UK | May 2020 | Case series | 3 | 35.6 | M 3 | AML 2, ALL 1 | daunorubicin 2, cytarabine 2, gemtuzumab ozogamicin 2, blinatumomab 1 | less than 1 y | RT‐PCR, CT scans | antibiotics 3, anakinra 3, IVIg 2, oxygen support 3 | Cough 2, rhinorrhea 1, sore throat 1, diarrhea 2, fever 3, rash 2, dyspnea 1 | Increased: Ferritin 3, triglycerides 3, CRP 1 Decreased: PLT 3, RBC 2, WBC 2, lymphocyte 1 | Previous seizures | Discharged 3 |
| Bellmann‐Weiler 44 | Austria | Jun 2020 | Case series | 3 | 65 | M 3 | AML 1, follicular lymphoma 1, hairy cell leukemia 1 | Bendamustine 1, rituximab 1 | 8y | RT‐PCR, CT scans | Oxygen support 3, physiotherapy 1, HCQ 1, AZ 1, favipiravir 2, antibiotics 1 | Fever 2, dyspnea 2, cough 3, asthenia 2, anorexia 1, diarrhea 1 | Increased: CRP, IL‐6 Decreased: WBC 3, lymphocyte 3, Hb, PLT | diabetes 1, hypertension 2, obesity 3, coronary heart disease 1 | Discharged 3 |
| Susek 45 | Sweden | Aug2020 | Original article | 9 | 70.4 | M 6 F 3 | MM 8, smoldering MM 1 | daratumumab 6, DEX 8, venetoclax 1, carfilzomib 1, bortezomib 1, lenalidomide 3 | NR | RT‐PCR | Oxygen support 4 | Fever 9, cough 8, dyspnea 3, diarrhea3, arthralgia3, ageusia 3 | Increased: CRP 5 Decreased: Hb 9, WBC 3, ANC 2, lymphocyte | Diabetes 4, hypertension 3, obesity 2 | Discharged 5 Died 4 |
| Ye 46 | China | Jul 2020 | Case report | 1 | 72 | F | CLL | NR | NR | RT‐PCR, CT scans | LPV/r, IFN, IVIg, ARB | Fever, cough | Increased: Lymphocyte, D‐dimer | NR | Discharged |
| Phillips 47 | US | Sep 2020 | Case report | 1 | 18 | M | ALL | vincristine, daunorubicin, mPDRL | NR | RT‐PCR | Oxygen support, corticosteroids, vasopressor | Fever, cough | Increased: WBC, LDH Decreased: Hb, PLT, hyperuricemia | AIHA | Discharge |
| Zamani 48 | Iran | Jan 2021 | Case report | 1 | 35 | F | AML | Chemotherapy | less than 1 y | RT‐PCR, CT scans | NR | Dyspnea, malaise, cough | NR | AMN | Death |
| Krengli 24 | Italy | Dec 2020 | Case report | 1 | 62 | F | MM | Bortezomib‐thalidomide‐DEX, cyclophosphamide, melphalan, radiotherapy, carfilzomib +DEX | 2y | RT‐PCR, CT scans | HCQ, darunavir‐cobicistat, oxygen support | Cough, fever, dysphagia | Increased: CRP Decreased: Hb | hypercholesterolemia, osteoporosis | Death |
| Kohla 49 | Qatar | Dec 2020 | Case report | 1 | 58 | M | Hairy Cell Leukemia | NR | 0y | RT‐PCR, CT scans | HCQ, AZ, tocilizumab, mPDRL, IVIg, vasopressors, antibiotics, oxygen support | Fever, fatigue, cough, dyspnea | Increase: Creatinine, ALT, AST, LDH, IL‐6, D‐dimer, ferritin Decrease: WBC, ANC, Hb, PLT | None | NR |
| Engelhardt, 50 | Germany | 2020 Jul | Cohort | 21 | 59 | M 17 F 4 | MM | daratumumab‐combination 5, elotuzumab‐combination 1, VCd/KRd 2/1, lenalidomide 3, none 9 | NR | RT‐PCR. | Antibiotics 17, AZ 4, HCQ 7, RDV 1, Tocilizumab 1, Anakinra 1, oxygen support 3 | Cough 17, fever 16, myalgia 4, GI symptoms 2 | NR | None 4, cardiac/ hypertension 11, renal impairment 3, obesity 1, PNP 4, diabetes 4, hypothyreosis 4 | Discharged 21 |
| Rusconi 51 | Italy | July 2020 | Case report | 1 | 62 | M | classical HL | ABVD | 2 y | RT‐PCR, CT scans | Levofloxacine, oxygen support, HCQ, LPV/r, enoxaparin, tocilizumab, CRO | Fever | Increased: Creatinine, fibrinogen, D‐dimer, CRP, LDH, ferritin Decreased: Lymphocyte | Hypertension, melanoma, papillary renal cell cancer | Discharged |
| Denis 52 | France | Jul 2020 | Case report | 1 | 72 | F | Mantle cell lymphoma | R‐CHOP | NR | RT‐PCR, CT scans | Kaletra, CRO | Confusion | NR | NR | NR |
| Moore 53 | US | Oct 2020 | Case report | 1 | 63 | F | non‐HL | obinutuzumab | NR | RT‐PCR | Plasma | Fever, myalgia, cough | Increased: CRP, LDH Decreased: WBC, lymphocyte | NR | Discharged |
| Vardanyan 54 | UK | Jul 2020 | Case report | 1 | 61 | F | CLL | NR | NR | RT‐PCR, CT scans | Oxygen support, amoxicillin‐clavulanic acid, TZP, clarithromycin, tocilizumab | Fever, dyspnea, cough, fatigue | Increased: D‐dimer, ferritin Decreased: Hb, WBC, lymphocyte | NR | NR |
| Abdalhadi 55 | Qatar | May 2020 | Case report | 1 | 65 | M | CML | Dasatinib | 4 y | RT‐PCR, CT scans | HCQ, AZ, OTV, TZP, oxygen support, LPV/r, tocilizumab, mPDRL | Fever, cough, chest pain | Increased: D‐dimer, CRP, LDH Decreased: ANC, Hb, PLT | NR | Discharged |
| Giammarco 56 | Italy | Dec 2020 | Case report | 1 | 50 | M | AML | all‐trans PRED | NR | RT‐PCR, CT scans | NR | Fever, ostealgia | Increased: LDH, creatine kinase, D‐dimer Decreased: ANC, PLT | None | Death |
| Li 57 | China | Dec 2020 | Case report | 1 | 61 | M | MM | bortezomib, DEX | 0 y | RT‐PCR, CT scans | Ceftazidime, oxygen support, IVIg, meropenem, teicoplanin, Ganciclovir, IFN, ARB, OTV, moxifloxacin | Fever, cough, chest pain, dyspnea | Increased: CRP, D‐dimer Decreased: Hb, lymphocyte | NR | Discharged |
| Marcia 58 | Italy | Jul 2020 | Case report | 1 | 3 | M | ALL | PRED, vincristine‐daunorubicin | NR | RT‐PCR, CT scans | Antibiotics, LPV/r, HCQ | Fever, epistaxis, weight loss, bruises, hepatosplenomegaly | Increased: WBC Decreased: Hb, PLT | NR | Discharged |
| Kamit 59 | Turkey | Nov 2020 | Case report | 1 | 9 | F | ALL | intrathecal‐IV methotrexate, vincristine, cyclophosphamide, cytosine arabinoside, L‐asparaginase, DEX | 0.5 y | RT‐PCR, CT scans | vancomycin, meropenem, trimethoprim–sulfamethoxazole, ganciclovir, oxygen support, IVIg, Favipiravir, hydrocortisone, tocilizumab, plasma | Fever, cough | Decrease: WBC, lymphocyte, ANC | Angelman syndrome | Death |
| Otsuka 60 | Japan | Nov 2020 | Case report | 1 | 56 | M | Mantle cell lymphoma | rituximab/cyclophosphamide/vincristine sulfate/doxorubicin, hydrochloride/DEX/methotrexate/cytarabine, bendamustine/rituximab | 2 y | RT‐PCR, CT scans | Favipiravir, antibiotic, cefepime, oxygen support, HCQ, VAN, TZP, IVIg, ciclesonide, meropenem, teicoplanin | Fever | Increased: AST, ALT, Decreased: WBC, lymphocyte, Hb, PLT | NR | Death |
| Bellesso 61 | Brazil | Mar 2021 | Case report | 1 | 76 | F | MM | Bortezomib, DEX, radiotherapy, daratumumab | 1.5 y | RT‐PCR | CRO, VAN, oxygen support, vasoactive drug, meropenem | Confusion, hip pain, respiratory distress | NR | ESRD, hypertension, glucose intolerance | Death |
| Glenthøj 62 | Denmark | Sep 2020 | Cohort | 66 | 66.7 | M 40 F 26 | MM 11, CLL 31, AML 8 | rituximab 14, daratumumab 4, purine analogues 7, ibrutinib 3, non‐cancer immunosuppressive treatment 5 | NR | RT‐PCR, CT scans | Oxygen support 42 | Fever 53, Cough 50, Dyspnea 22, Headache 11, Myalgia 6, Diarrhea 3 | Decreased: lymphocyte 27, ANC 4 | Obesity 8, smokers 3, heart disease 3, lung disease 9, diabetes 9, renal disease 7, liver disease 1 | Discharged 50 Death 16 |
| Wang 63 | US | July2020 | Cohort | 58 | 67 | M 30 F 28 | MM 54, smoldering MM 4 | daratumumab 28, immunomodulatory drugs 32, proteasome inhibitor 22, venetoclax 5, corticosteroids 30 | 2 y (29.8 months) | RT‐PCR | oxygen support 10, RDV 1, HCQ 17, AZ 17, antibiotics 19, corticosteroid 10, plasma 1, selinexor 5, anti‐IL‐6 4, anti‐IL‐1 2, anti TNF 1 | Fever 40, Cough 37, dyspnea 26 | Decreased: WBC 20, ANC 15, lymphocyte 7 | Hypertension 37, Hyperlipidemia 36, Obesity 21, Diabetes 16, chronic kidney disease 14, lung disease 12, current or former smoker 21, CAD and/or CVD 13, heart failure 7 | 44 Discharged Death 14 |
| Sánchez‐Jara 64 | Mexico | Mar2021 | Original article | 15 | 7.5 | M 8 F 7 | ALL 12, AML 3 | Chemotherapy | NR | RT‐PCR, CT scans | Oxygen therapy 13 | Fever 13, rhinorrhea 2, cough 9, headache 4, respiratory distress 8, seizures 1, irritability 4, sore throat 2, diarrhea 2, drowsiness 2 | Increased: CRP 13 Decreased: ANC 13, RBC 13, WBC 13, lymphocyte 14, PLT 13 | NR | Discharged 8 Death 7 |
| Garcia‐Suarez 65 | Spain | Oct 2020 | Observational study | 697 | 72 | NR | non‐HL 187, MM 136, CLL 109, HL 32, ALL 13, myelodysplastic syndrome 78, AML 61, CML 16, Ph‐negative myeloproliferative neoplasms 63 | Chemotherapy 169, molecular targeted therapies 81, immunomodulatory drugs 45, monoclonal antibodies 44, Hypomethylating agents 33, none 286 | NR | RT‐PCR | HCQ 558, AZ 276, antiretrovirals 337, IFN 50, corticosteroid 318, tocilizumab 132 | NR | NR | Hypertension 277, cardiac disease 138, diabetes 121, renal disease 77, pulmonary disease 90 | Discharged 467 Death 230 |
| Martinez‐Lopez 66 | Spain | Oct 2020 | Case series | 167 | 71 | M 95 F 72 | MM 167 | Proteasome inhibitor 138, immunomodulatory drug 119, monoclonal antibody 38 | >18 m 112, <18 m 55 | RT‐PCR | HCQ 148, AZ 91, antiretrovirals 103, steroids 83, Anti‐interleukin‐6 receptor antibody therapy 22, heparin 109, oxygen support 128 | NR | NR | None 41, cardiac disease 35, pulmonary disease 23, diabetes 28, renal disease 32, hypertension 67 | Discharged 111 Death 56 |
| Regalado‐Artamendi 67 | Spain | Feb 2021 | Original article | 177 | 70 | M 99 F 78 | HL 19, follicular lymphoma 62, DLBCL 39, other aggressive lymphomas 27, other indolent lymphomas 30 | CD20‐chemotherapy 58, CD20‐bendamustine 20, Chemotherapy 33, Molecular targets 3, Immunotherapy 38 | NR | RT‐PCR | LPV/r 89, HCQ 156, IFN 13, AZ 79, RDV 9, plasma 7, tocilizumab 51, anakinra 11, mPDRL 65, DEX 20, oxygen support 125 | Fever 134, cough 115, dyspnea 87, myalgia 45, diarrhea 36, chest pain 25, rhinorrhea 15, anosmia 14, sore throat 7 | NR | Heart disease 34 Hypertension 73 Diabetes 33, Obesity 14, Dyslipidemia 27, Chronic pulmonary disease 23, Asthma 9, Chronic kidney disease 11, Chronic liver disease 4 | Discharged 116 Death 61 |
| Yigenoglu 17 | Turkey | Aug2020 | Cohort | 740 | 56 | M 397 F 343 | HL 27, CLL 54, MM 77, ALL 18, myeloproliferative neoplasm 116, CML 30, non‐HL 223, Myelodysplastic syndrome 146, AML 40, hairy cell leukemia 9 | NR | NR | RT‐PCR | Favipiravir 189, OTV 309, LPV/r 35, HCQ 508 | NR | NR | Hypertension 379, diabetes 198, cardiovascular disease 156, respiratory disease 175 | Discharged 701 Death 39 |
| Piñana 68 | Spain | Aug 2020 | Observational study | 367 | 64 | M 225 F 142 | Non‐HL 91, AML 67, ALL 25, Myelodysplastic syndrome 22, chronic myeloproliferative disease 29, CLL 4 | NR | NR | RT‐PCR | AZ 156, HCQ 147, LPV/r 163, RDV 8, corticosteroid 10, tocilizumab 50, anakinra 18, baricitinib 7 | None 30, fever 259, rhinorrhea 54, pharyngitis 27, fatigue 196, myalgia 73, cough 244, diarrhea 81, vomiting 37 | Increased: CRP 200, D‐dimer 172, ferritin 119 Decreased: ANC 48, lymphocyte 140 | Smoking 33, hypertension 142, cardiomyopathy 65, dyslipidemia 94, diabetes 86 | Discharged 262 Death 105 |
| de la Cruz‐Benito 69 | Spain | August 2020 | Cohort | 1 | 52 | F | DLBCL | R‐CHOP | NR | RT‐PCR | NR | NR | Decreased: Lymphocyte | Dyslipidemia | NR |
| Başcı 70 | Turkey | July2020 | Original article | 16 | 51 | M 6 F 10 | CML 16 | Imatinib 9, Nilotinib 3, Dasatinib 4 | NR | RT‐PCR | Favipiravir 4, OTV 9, LPV/r 1, HCQ 13 | NR | NR | None 5, COPD 4, diabetes 3, hypertension 7, CAD 5, chronic renal disease 2, CVD 1 | NR |
| Naseri 71 | Iran | Oct 2020 | Case report | 1 | 42 | F | AML | Idarubicin, cytarabine | new | RT‐PCR, CT scans | Oxygen support, linezolid, meropenem, LPV/r, IFN | Fever, dyspnea, myalgia | Increased: CRP, ferritin, LDH, D‐dimer Decreased: WBC, Hb, PLT, ANC, lymphocyte | Diabetes | Death |
| Song 72 | China | Dec 2019 | Case report | 1 | 78 | F | CLL | None | 5 y | RT‐PCR, CT scans | OTV, cefoperazone, sulbactam, linezolid, mPDRL, oxygen support | Fatigue, malaise, hyporexia | Increased: WBC, lymphocyte, CRP Decreased: Hb | Hypertension, cardiovascular disease, COPD | Death |
| Li 73 | China | May 2020 | Case report | 1 | 26 | M | B‐cell lymphoma | DA‐EPOCH‐R | NR | RT‐PCR, CT scans | Meropenem, linezolid, AZ, ganciclovir, OTV, ARB | Fever | Decreased: ANC, lymphocyte | None | Discharged |
| Baldacini 74 | France | May 2020 | Case report | 1 | 62 | F | AML | NR | less than 1 y | RT‐PCR, CT scans | NR | Asthenia, dyspnea, epistaxis | Increased: WBC, CRP, D‐dimer Decreased: Hb, PLT, ANC | NR | Death |
| Farmer 75 | UK | Jun 2020 | Case report | 1 | 36 | M | AML | Arsenic trioxide | less than 1 y | RT‐PCR | NR | Fever, cough, sweats | Increased: D‐dimer, ferritin, creatinine, LDH, CRP Decreased: WBC, Hb, ANC, lymphocyte, PLT | NR | NR |
| Puyo 76 | Spain | Jan 2020 | Case report | 1 | 20 months | M | ALL | Chemotherapy | 2 months | RT‐PCR | TZP, amikacin, oxygen support, HCQ, AZ, VAN, tocilizumab | Fever | Decreased: ANC | NR | Discharged |
| Malek 77 | US | Jul 2020 | Case report | 1 | 41 | F | CLL | NR | NR | RT‐PCR, CT scans | Cefepime, linezolid, DOX, mPDRL, oxygen support | Fever, nausea, vomiting, diarrhea, cough, dyspnea, myalgia | Increased: WBC, Lymphocyte, ALT, AST, CRP, D‐dimer, LDH, ferritin | Obesity | Discharged |
| Schied 78 | US | Sep 2020 | Case report | 1 | 6 | F | B lymphoblastic lymphoma | Chemotherapy | NR | RT‐PCR | Supportive care | None | Increased: Ferritin | NR | Discharged |
| Pandrowala 79 | US | Mar 2021 | Case report | 1 | 5 | F | AML | Daunorubicin, cytarabine, fludarabine, idarubicin, ventoclax, 5‐azacytidine | NR | RT‐PCR | Oxygen support, mPDRL, meropenem, amikacin | Fever | Increased: WBC, CRP Decreased: Hb, ANC, PLT | NR | Discharged |
| Rathore 80 | India | Jun 2020 | Case report | 1 | 10 | M | ALL | Chemotherapy | 3 months | RT‐PCR | DEX | Cough | NR | NR | Discharged |
| Zhang 81 | China | Apr 2020 | Case report | 1 | 60 | M | MM | Bortezomib, thalidomide, DEX | 5 y | RT‐PCR, CT scans | Moxifloxacin, ARB, oxygen support | Chest tightness, dyspnea | Increased: CRP Decreased: Lymphocyte | NR | Discharged |
| Ghandili 32 | Germany | Dec 2020 | Case series | 12 | 60 | M 9 F 3 | AML 8, ALL 3, lymphoblastic lymphoma 1 | NR | NR | RT‐PCR | Oxygen support 5, LPV/r 1, pentaglobin 2, plasma 1, tocilizumab 1, None 5 | None 4 | Decreased: ANC 12, lymphocyte 12 | Hypothyroidism 1, Asthma 1, allergic rhinitis 1, smoker 1 | Discharged 10 Death 2 |
| Kos 82 | Germany | Sep 2020 | Case report | 1 | 72 | M | Marginal zone lymphoma | Bendamustine, rituximab | NR | RT‐PCR | Ampicillin, sulbactam, meropenem, clarithromycin, IVIg | Fever, cough | Increased: CRP, LDH Decreased: Hb | None | Discharged |
| Nunez Torron 83 | Spain | Jun 2020 | Cohort | 4 | 54.5 | M 3 F 1 | AML 4 | Chemotherapy | new | RT‐PCR, CT scans | HCQ 4, LPV/r 3, AZ 1, corticosteroids 3, tocilizumab 2, oxygen support 4 | Fever 4, cough 1, asthenia 1 | Increased: WBC 1 Decreased: Hb 1, PLT 1 | None 4 | Discharged 1 Death 3 |
Demographic, clinical and laboratory findings
The demographic information, clinical features, and laboratory findings in COVID‐19 patients with hematological malignancies are shown in Tables 2 and 3 . The results of laboratory data showed that ALT, AST, CRP, and LDH tests have increased in COVID‐19 patients with hematological malignancies. However, hemoglobin level, platelet count, lymphocyte count, and RBC decreased in these patients. The majority of patients were male (56.73%). Fever (74.24%), cough (67.64%), and fatigue (53.19%) were the most common clinical manifestations among the included patients.
TABLE 2
Summary of the findings in COVID‐19 patients with hematological malignancies
Abbreviations: ABVD, adriamycin, bleomycin, vinblastine, dacarbazine; AIHA, autoimmune hemolytic anemia; ALL, acute lymphoblastic leukemia; ALT, alanine aminotransferase; AML, acute myeloid leukemia; AMN, acute macular neuroretinopathy; ANC, absolute neutrophil count; ARB, arbidol; AST, aspartate aminotransferase; AZ, azithromycin; BEACOPP, bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisolone; CHOP, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (oncovin), and prednisone; CLL, Chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CRO, ceftriaxone; CRP, C‐reactive protein; CXR, chest X‐ray; DLBCL, diffuse large B‐cell lymphoma; DOX, doxycycline; EBV, Epstein‐Barr virus; HB, hemoglobin; HCQ, hydroxychloroquine; HGBL, high grade B‐cell lymphoma; HL, Hodgkin lymphoma; IBR, ibrutinib; ICE, ifosfamide, carboplatin, etoposide; IFN, interferon; IFRT, involved field radiotherapy; IV, intravenous; Ig, immunoglobulin; LDH, lactate dehydrogenase; LPV, lopinavir; LPV/r, lopinavir/ritonavir; MM, multiple myeloma; mPDRL, methylprednisolone; NR, not reported; OTV, oseltamivir; PLT, platelet; PRED, prednisone; RTV, ritonavir; RDV, remdesivir; TZP, piperacillin/tazobactam; VAN, vancomycin; VCd/KRd:bortezomib‐cyclophos‐phamid‐dexamethasone/carfilzomib‐lenalidomide‐dexamethasone.
| n / n (%) | No. of studies that mentioned | |
| Gender | ||
| Male | 962/1698 (56.65%) | 53 |
| Female | 736/1698 (43.35%) | |
| Treatment of blood cancer | ||
| Proteasome inhibitor | 160/521 (30.71%) | 5 |
| Chemotherapy | 209/891 (23.46%) | 11 |
| Immunotherapy | 239/1175 (20.34%) | 7 |
| Monoclonal antibodies | 140/1051 (13.32%) | 6 |
| Daratumumab | 44/442 (9.95%) | 7 |
| Molecular targeted therapy | 84/884 (9.50%) | 2 |
| Corticosteroids | 47/371 (12.66%) | 13 |
| Rituximab | 19/370 (5.14%) | 10 |
| Bendamustine | 23/478 (4.81%) | 7 |
| Hypomethylating agents | 33/707 (4.67%) | 3 |
| Imatinib | 10/313 (3.19%) | 5 |
| Lenalidomide | 7/319 (2.19%) | 5 |
| Purine analogues | 7/362 (1.93%) | 4 |
| Bortezomib | 6/311 (1.92%) | 9 |
| Ventoclax | 7/364 (1.91%) | 6 |
| Vincristine | 5/301 (1.66%) | 6 |
| Cytarabine | 5/302 (1.65%) | 7 |
| Daunorubicin | 5/302 (1.65%) | 7 |
| Dasatinib | 5/313 (1.60%) | 2 |
| Cyclophosphamide | 4/301 (1.33%) | 8 |
| Nilutinib | 3/312 (0.96%) | 4 |
| Ibrutinib | 3/362 (0.82%) | 4 |
| ABVD | 2/298 (0.67%) | 5 |
| Idarubicin | 2/298 (0.34%) | 5 |
| L‐asparginase | 2/298 (0.67%) | 5 |
| Methotrexate | 2/298 (0.67%) | 5 |
| Pembrolizumab | 2/298 (0.67%) | 5 |
| Radiotherapy | 2/298 (0.67%) | 5 |
| R‐CHOP | 2/298 (0.67%) | 5 |
| Thalidomide | 2/298 (0.67%) | 5 |
| Gemtuzumab ozogamicin | 2/299 (0.66%) | 4 |
| Carfilzomib | 2/306 (0.65%) | 5 |
| VCd | 2/308 (0.64%) | 4 |
| 5‐Azacytidine | 1/297 (0.34%) | 4 |
| Arsenic trioxide | 1/297 (0.34%) | 4 |
| BEACOPP | 1/297 (0.34%) | 4 |
| Brentuximab | 1/297 (0.34%) | 4 |
| Cytosine arabinose | 1/297 (0.34%) | 4 |
| DA‐EPOCH | 1/297 (0.34%) | 4 |
| Doxorubicin | 1/297 (0.34%) | 4 |
| Hydrochloride | 1/297 (0.34%) | 4 |
| Fludarabine | 1/297 (0.34%) | 4 |
| ICE | 1/297 (0.34%) | 4 |
| IFRT | 1/297 (0.34%) | 4 |
| Melphalan | 1/297 (0.34%) | 4 |
| mPDRL | 1/297 (0.34%) | 4 |
| Obinutuzumab | 1/297 (0.34%) | 4 |
| Panobinostat | 1/297 (0.34%) | 4 |
| Vedotin | 1/297 (0.34%) | 4 |
| Blinatumomab | 1/299 (0.33%) | 4 |
| Elotuzumab | 1/308 (0.32%) | 4 |
| KRd | 1/308 (0.32%) | 4 |
| COVID‐19 treatment & ancillary medications | ||
| Hydroxychloroquine (HCQ) | 1571/2267 (69.30%) | 23 |
| Oxygen support | 365/559 (65.30%) | 36 |
| Anticoagulant therapy | 112/175 (64%) | 5 |
| Meropenem | 8/13 (61.54%) | 9 |
| IV immunoglobulin (IVIg) | 8/14 (57.14%) | 8 |
| Antiretrovirals | 440/869 (50.63%) | 2 |
| Ceftriaxone (CRO) | 5/10 (50%) | 6 |
| Piperacillin/tazobactam (TZP) | 5/10 (50%) | 6 |
| Antibiotics | 44/94 (46.81%) | 8 |
| Arbidol (ARB) | 4/9 (44.44%) | 5 |
| Linezolid | 4/9 (44.44%) | 5 |
| Vancomycin (VAN) | 4/9 (44.44%) | 5 |
| Corticosteroid therapy | 429/1009 (42.52%) | 10 |
| Oseltamivir (OTV) | 323/766 (42.17%) | 8 |
| Azithromycin (AZ) | 633/1502 (42.14%) | 16 |
| Methylprednisolone (mPDRL) | 73/190 (38.42%) | 11 |
| Amoxicillin/clavulanate | 3/8 (37.50%) | 4 |
| Doxycycline (DOX) | 3/8 (37.50%) | 4 |
| Ganciclovir | 3/8 (37.50%) | 4 |
| Vasoactive drugs (including vasopressor) | 3/8 (37.50%) | 4 |
| Supportive therapy | 3/10 (30%) | 4 |
| Amikacin | 2/7 (28.57%) | 3 |
| Cefepime | 2/7 (28.57%) | 3 |
| Clarithromycin | 2/7 (28.57%) | 3 |
| Levofloxacin | 2/7 (28.57%) | 3 |
| Moxifloxacin | 2/7 (28.57%) | 3 |
| Paracetamol | 2/7 (28.57%) | 3 |
| Sulbactam | 2/7 (28.57%) | 3 |
| Teicoplanin | 2/7 (28.57%) | 3 |
| Favipiravir | 198/830 (23.85%) | 7 |
| Lopinavir/ritonavir (LPV/r) | 300/1324 (22.66%) | 14 |
| Tocilizumab | 245/1286 (19.05%) | 13 |
| Ampicillin | 1/6 (16.67%) | 2 |
| Cefoperazone | 1/6 (16.67%) | 2 |
| Ceftazidime | 1/6 (16.67%) | 2 |
| Ciclesonide | 1/6 (16.67%) | 2 |
| Darunavir‐cobicistat | 1/6 (16.67%) | 2 |
| Kaletra | 1/6 (16.67%) | 2 |
| Pentaglobin | 2/12 (16.67%) | 1 |
| RBC transfusion | 1/6 (16.67%) | 2 |
| Ribavirin | 1/6 (16.67%) | 2 |
| Trimethoprim–sulfamethoxazole | 1/6 (16.67%) | 2 |
| Anti‐IL‐6 | 26/240(10.83%) | 3 |
| Selinexor | 5/63 (7.93%) | 2 |
| Interferon (IFN) | 67/883 (7.59%) | 6 |
| Anakinra | 33/573 (5.76%) | 5 |
| Plasma | 11/249 (4.42%) | 5 |
| Anti‐IL‐2 | 2/63 (3.17%) | 2 |
| Remdesivir (RDV) | 19/628 (3.03%) | 4 |
| Baricitinib | 7/372 (1.88%) | 2 |
| Anti TNF | 1/63 (1.59%) | 2 |
| Clinical manifestations | ||
| Fever | 562/757 (74.24%) | 38 |
| Cough | 508/751 (67.64%) | 30 |
| Fatigue | 200/376 (53.19%) | 7 |
| Dyspnea | 155/366 (42.34%) | 23 |
| Myalgia | 131/639 (20.50%) | 7 |
| Respiratory distress | 9/51 (17.65%) | 5 |
| Diarrhea | 48/309 (15.53%) | 10 |
| Chest pain or tightness | 28/215 (13.02%) | 7 |
| Headache | 15/116 (12.93%) | 5 |
| Rhinorrhea | 72/567 (12.70%) | 6 |
| Vomiting | 38/373 (10.19%) | 4 |
| Asthenia | 4/43 (9.30%) | 6 |
| Irritability | 4/50 (8%) | 4 |
| Pharyngitis | 27/372 (7.26%) | 3 |
| Ageusia | 3/44 (6.82%) | 4 |
| Arthralgia | 3/44 (6.82%) | 4 |
| Anosmia | 14/212 (6.60%) | 4 |
| Confusion | 2/37 (5.41%) | 5 |
| Epistaxis | 2/37 (5.41%) | 5 |
| Hypoxia | 2/37 (5.41%) | 4 |
| Malaise | 2/37 (5.41%) | 5 |
| Nausea | 2/37 (5.41%) | 5 |
| Rash | 2/37 (5.41%) | 4 |
| Sore throat | 12/232 (5.17%) | 8 |
| Anorexia or Hyporexia | 2/39 (5.13%) | 5 |
| Drowsiness | 2/50 (4%) | 4 |
| Gastrointestinal symptoms | 2/56 (3.57%) | 4 |
| Body aches | 1/36 (2.78%) | 4 |
| Bruises | 1/36 (2.78%) | 4 |
| Chills | 1/36 (2.78%) | 4 |
| Dysphagia | 1/36 (2.78%) | 4 |
| Hypoxemia | 1/36 (2.78%) | 4 |
| Orthopnea | 1/36 (2.76%) | 4 |
| Ostealgia | 1/36 (2.78%) | 4 |
| Rectal bleeding | 1/36 (2.78%) | 4 |
| Rigors | 1/36 (2.78%) | 4 |
| Sweats | 1/36 (2.78%) | 4 |
| Weight loss | 1/36 (2.78%) | 4 |
| Seizures | 1/50 (2%) | 4 |
| Laboratory findings | ||
| Increased | ||
| ALT | 3/3 (100%) | 3 |
| ANC | 2/2 (100%) | 2 |
| AST | 3/3 (100%) | 3 |
| bilirubin | 2/2 (100%) | 1 |
| Creatine kinase | 1/1 (100%) | 1 |
| Creatinine | 2/2 (100%) | 2 |
| Fibrinogen | 2/2 (100%) | 2 |
| IL‐6 | 3/3 (100%) | 2 |
| IL‐8 | 1/1 (100%) | 1 |
| LDH | 16/16 (100%) | 16 |
| Lymphocyte | 7/7 (100%) | 7 |
| Monocyte | 1/1 (100%) | 1 |
| Reticulocyte | 1/1 (100%) | 1 |
| Triglycerides | 3/3 (100%) | 1 |
| WBC | 10/13 (76.92%) | 10 |
| CRP | 242/417 (58.03%) | 26 |
| D‐dimer | 189/384 (49.22%) | 17 |
| Ferritin | 134/382 (35.08%) | 13 |
| Decreased | ||
| Albumin | 1/1 (100%) | 1 |
| Uric acid | 1/1 (100%) | 1 |
| Hb | 29/32 (90.62%) | 21 |
| PLT | 31/36 (86.11%) | 17 |
| RBC | 15/18 (83.33%) | 2 |
| WBC | 50/97 (51.55%) | 14 |
| Lymphocyte | 218/538 (40.52%) | 20 |
| ANC | 105/538 (19.52%) | 17 |
TABLE 3
The main findings in COVID‐19 patients with hematological malignancies categorized based on the type of malignancy
Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, Chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CRP, C‐reactive protein; HCQ, hydroxychloroquine; HL, Hodgkin lymphoma; LDH, lactate dehydrogenase; LPV/r, lopinavir/ritonavir; MM, multiple myeloma; PLT, platelet.
| Total (%) | ALL | AML | CLL | CML | HL | NHL | MM | MDS | MPN | |
| Patients | 2395 | 77 (4.19) | 200 (9.16) | 214 (13.60) | 64 (4.40) | 80 (4.95) | 614 (30.01) | 486 (27.55) | 246 (13.63) | 208 (11.53) |
| Treatment of blood cancer | ||||||||||
| Chemotherapy | 209 (23.46) | 20 (76.92) | 28 (41.27) | 4 (2.15) | 2 (12.5) | 21 (41.17) | 83 (34.15) | 33 (24.26) | 2 (2.56) | 31 (49.21) |
| Immunotherapy | 239 (20.34) | – | – | – | – | 7 (36.84) | 20 (13.69) | 196 (54.29) | – | – |
| Monoclonal antibodies | 140 (13.32) | – | – | 1 (0.54) | – | – | 25 (13.37) | 52 (17.17) | – | – |
| Molecular targeted therapy | 84 (9.50) | – | 3 (4.91) | 28 (15.05) | 14 (87.5) | – | 8 (3.32) | 12 (8.82) | ‐ | 18 (28.57) |
| Hypomethylating agent | 33 (4.67) | – | 17 (27.87) | – | – | – | 1 (0.53) | – | 15 (19.23) | – |
| COVID‐19 treatment | ||||||||||
| Oxygen support | 365 (65.30) | 2 (100) | 17 (73.92) | 27 (69.23) | 2 (100) | 2 (100) | 5 (100) | 157 (57.72) | – | – |
| HCQ | 1571 (69.30) | 2 (100) | 5 (41.67) | 3 (100) | 15 (83.33) | 2 (100) | 2 (100) | 173 (70.04) | – | – |
| Antibiotics | 44 (46.81) | 2 (100) | 2 (22.22) | 1 (100) | – | 1 (100) | 1 (100) | 36 (45.57) | – | – |
| Corticosteroids | 429 (42.52) | 1 (100) | 3 (75) | 1 (100) | – | 1 (100) | 1 (100) | 93 (41.33) | – | – |
| LPV/r | 300 (22.66) | 2 (50) | 4 (33.33) | 2 (100) | 3 (16.67) | 2 (100) | – | – | – | – |
| Clinical manifestations | ||||||||||
| Fever | 562 (74.24) | 15 (71.42) | 20 (90.91) | 33 (82.5) | 2 (100) | 2 (100) | 6 (84.71) | 78 (75.73) | – | – |
| Cough | 508 (67.64) | 11 (50) | 12 (5.89) | 32 (82.05) | 2 (100) | 1 (100) | 5 (83.34) | 73 (70.87) | – | – |
| Dyspnea | 155 (42.34) | 1 (6.25) | 4 (36.36) | 19 (48.71) | – | – | 4 (80) | 33 (41.25) | – | – |
| Diarrhea | 48 (15.53) | 1 (6.25) | 3 (60) | 5 (15.15) | – | – | – | 3 (33.33) | – | – |
| Respiratory distress | 9 (17.65) | 6 (37.5) | 1 (33.33) | – | – | – | – | 1 (100) | – | – |
| Laboratory findings ‐ increase | ||||||||||
| LDH | 16 (100) | 1 (100) | 2 (100) | 3 (100) | 2 (100) | 2 (100) | 4 (100) | – | – | – |
| CRP | 242 (58.03) | 1 (100) | 4 (100) | 5 (100) | 1 (100) | 2 (100) | 5 (100) | 9 (69.23) | – | – |
| D‐dimer | 189 (49.22) | ‐ | 3 (100) | 4 (100) | 2 (100) | 1 (100) | 2 (100) | 3 (100) | – | – |
| Ferritin | 134 (35.08) | 1 (100) | 4 (100) | 4 (100) | 1 (100) | 1 (100) | 1 (100) | 2 (100) | – | – |
| Laboratory findings – decrease | ||||||||||
| Hb | 29 (90.62) | 2 (100) | 5 (62.5) | 5 (100) | 1 (100) | ‐ | 5 (100) | 10 (100) | – | – |
| PLT | 31 (86.11) | 3 (100) | 7 (70) | 2 (100) | 1 (100) | 1 (100) | 3 (100) | – | – | – |
| WBC | 50 (51.55) | 2 (100) | 3 (75) | 4 (100) | – | – | 4 (100) | 23 (34.33) | – | – |
| Lymphocyte | 218 (40.52) | 1 (100) | 2 (100) | 3 (100) | – | 2 (100) | 6 (100) | 14 (19.72) | – | – |
| Gender | ||||||||||
| Male | 962 (56.65) | 20 (58.82) | 21 (65.62) | 24 (60) | 8 (44.44) | 13 (61.90) | 61 (53.98) | 158 (58.09) | 51 (65.38) | 43 (68.25) |
| Female | 736 (43.35) | 14 (41.18) | 11 (34.38) | 16 | 10 (55.56) | 8 (38.01) | 52 (46.02) | 114 (41.91) | 27 (34.62) | 20 (31.75) |
Treatments for COVID‐19 and hematological malignancies
The treatment options for COVID‐19 patients with hematological malignancies are summarized in Tables 2 and 3 . Hydroxychloroquine (69.3%), oxygen therapy (65.3%), and anticoagulant therapies (64.0%) such as enoxaparin and heparin were the most administrated treatments options for COVID‐19. On the contrary, proteasome inhibitors (30.71%) and chemotherapy (23.46%) were the most used therapeutics to cure different types of blood cancer among patients with hematological malignancies.
Comorbidities and mortality rate
Figure 2 shows a forest plot for the mortality rate in COVID‐19 patients with hematological malignancies. Based on a random‐effects model, the pooled estimate of death and discharge percent were 21.34% (95% CI: 11.24 to 33.11) and 77.60% (95% CI: 65.60 to 87.96), respectively. It means that more than three‐quarters of cases with COVID‐19 and hematological malignancy were survived during hospitalization. In addition, Figure 3 shows the prevalence of comorbidities among patients with hematological malignancies and SARS‐CoV‐2 infection. The most prevalent comorbidity was hypertension (44.61%; 95% CI: 39.94 to 49.28), and the less one was liver disease (1.96%; 95% CI: 0.05 to 3.88). The prevalence of other comorbidities is shown also in Figure 2 . We were interested in assessing the effect of age on the death rate in patients with COVID‐19 and malignancy (Figure 4 ). The meta‐regression demonstrated no significant association between death rate with age ( p = 0.513).
Risk of bias assessment
The results of the critical appraisal (JBI checklist) of included studies are summarized in Table S1 . Overall, 53 articles were identified as having a low risk of bias (quality assessment score > 7).
DISCUSSION
Since the onset of the COVID‐19 outbreak, several studies have reported the effects of COVID‐19 on cancer patients. In this regard, there is growing evidence that patients with a history of cancer have a higher rate of COVID‐19 mortality than individuals without cancer. In addition, it has been reported that patients with hematological cancers had the highest frequency of major adverse events. 5 , 12
Yeo et al. indicated that the cancer was associated with a 2.84‐fold increased risk of severe illness in COVID‐19 patients and a 2.60‐fold increased risk of death. 13 The prevalence of cancer in COVID‐19 patients is very low. In a recent study, the pooled prevalence of cancer in COVID‐19 patients was 2%. 14 , 15
Also, the results of the same studies from China and the United States of America reported that about 1–2% and 6% of COVID‐19 patients had cancer, respectively. 14 , 16
The prevalence of hematological malignancies among COVID‐19 patients has not yet been well studied. In a related study conducted by Yigenoglu et al. in Turkey, it has been reported that 0.39% of the COVID‐19 patients had hematological malignancy. The most common hematological malignancies were non‐Hodgkin lymphoma (30.1%) followed by myelodysplastic syndromes (19.7%). They reported that about 5.27% of the patients have died. 17
In the other study conducted by Mehta et al. 18 in New York, the mortality rate in lymphoid neoplasms was higher than the myeloid malignancies (35% vs. 43%). Our results estimated that the mortality rate in COVID‐19 patients with hematological malignancies was 21.34%. This discrepancy observed in the results of these studies can be due to different sizes of studies. Therefore, the results of studies conducted in all areas highlight the urgent need to pay special attention to patients with hematologic malignancy infected with COVID‐19.
The progression of blood malignancies is usually accompanied by a weakening of the immune system, which is initiated by the disease and continues through the strategy of anti‐tumor therapies such as chemotherapy and radiation therapy Therefore, the suppressed immune system may lead to a greater vulnerability of cancer patients to COVID‐19.
A previous study showed that anti‐tumor therapy increased the risk of dangerous symptoms within 14 days of the diagnosis of COVID‐19 and recommended that cancer patients with COVID‐19 avoid treatments that suppress the immune system. 19
On the hand, cytotoxic chemotherapies cause neutropenia and lymphocytopenia that aggravate the immunosuppressive status. This status leads to high infection rates and poor prognosis. 20 , 21 , 22
There is currently no advice on the effectiveness of conventional and targeted treatment strategies in these patients. 23
Hence, the risk–benefit ratio of these treatment strategies remains a challenge. In this regard, it has been demonstrated that radiation therapy has no higher risk of severe events related to the COVID‐19 for these patients. 5
For example, Krengli et al. 24 reported that radiation therapy could be considered a treatment strategy in COVID‐19 patients affected by myeloma. Recently, Liu et al. 25 demonstrated that patients with hematological malignancies were at a higher risk of death if they received chemotherapy 3 months before the COVID‐19 diagnosis.
It is recommended that the cancer treatment strategies be postponed until the radiological and clinical symptoms of COVID‐19 have been completely disappeared. 26 , 27 These clinical symptoms were previously mostly treated by hydroxychloroquine. However, recently, WHO recommended healthcare systems cease the use of this drug. 28 , 29
The most common complications of COVID‐19 are fever, dyspnea, cough, muscle ache, confusion, headache, pneumonia, acute respiratory distress, and acute respiratory failure. 30
The findings of the present study show that the highest incidence of clinical manifestations in patients with hematologic malignancy infected with SARS‐CoV‐2 belonged to fever (74.24%), cough (67.64%), fatigue (53.19%), dyspnea (42.47%), myalgia (20.50%), and the respiratory distress (17.65%). These results are consistent with those of other studies and confirm that pulmonary symptoms are the main clinical manifestations of COVID‐19 in more than half of the patients treated for the hematologic malignancies. 31
Our results demonstrated that the most common comorbidities in patients with COVID‐19 and hematological malignancies were hypertension (44.61%) and dyslipidemia (32.13%). In addition, it revealed that the patients who died had more comorbidities. Also, it has been shown that the mortality rate of these patients is related to the disease status, the status of the immune system, and the level of inflammation.
The elevated levels of C‐reactive proteins were observed in 58.03% of patients with hematologic malignancy infected with SARS‐CoV‐2. Also, other laboratory findings such as the increased d‐dimer levels (49.22%), neutropenia (19.52%), and the increase in bilirubin levels were seen in these patients. It seems that laboratory findings on admission can help predict the severity of COVID‐19 in patients with hematologic malignancy. Furthermore, it has been demonstrated that the monitoring of RNA load in plasma can be useful to anticipate the COVID‐19 outcomes in these patients. Ghandili et al. 32 reported that the increasing RNA titer is associated with the fatal outcomes in patients with acute myeloid leukemia infected SARS‐CoV‐2.
There are several limitations to this study. First, as our search was restricted to articles published in English, we might have missed some relevant publications in other languages. Second, only case series and research articles were enrolled in the meta‐analysis. Therefore, the existence of publication bias should be considered. Third, this study included patients whose RT‐PCR tests were positive for SARS‐CoV‐2. However, it is confirmed that false‐negative and false‐positive RT‐PCR may occur due to low amounts of SARS‐CoV‐2 concentrations and cross‐reaction with something that’s not SARS‐CoV‐2, respectively. Forth, heterogeneity in the study population selection and the retrospective characteristics was observed in the studies. Although the random‐effects model was assumed to reflect the similarity, there may still be differences of opinion. Fifth, all included studies have reported hospitalized patients. Due to these cases usually having a severe or moderate stage of disease, mild cases may be missed.
CONCLUSIONS
In this study, we reviewed the literatures reporting the COVID‐19 outcomes in patients with hematological malignancies. Our study reveals that about one‐quarter of patients with COVID‐19 and hematological malignancy have died during hospitalization. One of the most important reasons that confirm these patients are more vulnerable is their immune system dysfunction. Furthermore, anti‐cancer therapies may worsen their conditions. Therefore, the management of COVID‐19 in patients with hematological malignancies requires much more attention.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
AUTHOR CONTRIBUTIONS
Adel Naimi, Ilya Yashmi, Reza Jebeleh, Mohammad Imani Mofrad, Shakiba Azimian Abhar, Yasaman Jannesar, and Mohsen Heidary contributed in revising and final approval of the version to be published. All authors agreed and confirmed the study for publication.
Supporting information
Table S1
Click here for additional data file.
DATA AVAILABILITY STATEMENT
The authors confirm that the data supporting the results of this study is available within the article.
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