Table 1. Population, Intervention, Comparison, Outcome, and Study Types.

From: Efficacy of COVID-19 Vaccines in Patients with Hematological Malignancy Compared to Healthy Controls: A Systematic Review and Meta-analysis

Characteristics Inclusion Exclusion
Population Adult participants over 18 years with hematological malignancy and had received at least one dose of the COVID-19 vaccine. Patients with any other diseases and/or any group other than healthy populations.
Intervention (Exposure) First, second, or booster doses of COVID-19 vaccination Nonvaccinated population
Comparison Immune response to COVID-19 vaccination in patients with hematological malignancies and healthy control group. Immunoglobulin G (IgG) level, Neutralizing antibody (nAb) level Any malignancy other than patients with hematological malignancies, i.e., solid tumor.
Outcome Rates of seropositivity after one or two doses of COVID-19 vaccine, rates of positive nAb response after one or two doses of vaccine. Side effects (if any) of the vaccines on the exposed and healthy group, cross-classification of the rates of seropositivity, and rates of positive nAb response with respect to other potential confounders.
Study type All types of observational studies, experimental studies, and clinical trials. Incomplete studies, studies not reporting any antibody level, and studies reporting CD4 and CD8 cell count in response to COVID-19 vaccination.
Table 2. Search Strategies.

From: Efficacy of COVID-19 Vaccines in Patients with Hematological Malignancy Compared to Healthy Controls: A Systematic Review and Meta-analysis

Characteristics Description
Databases Medline via PubMed
EMBASE
WHO COVID-19 Research Database
Cochrane Library
Other searches Manual search using Keywords in Google Scholar
Reference list from selected articles
Boolean operators AND
OR
Antibody or seroconversion-related keywords, MeSH terms “Antibody formation”
“Seroconversion”
“Antibodies, neutralizing”
“Neutralizing Antibodies”
“seropositive*”
“seroconversion*”
“Antibody produce*”
“Antibody response*”
“Neutralizing antibody*”
Hematologic malignancy-related keywords, MeSH terms “Primary Myelofibrosis”
“Polycythemia Vera”
“Myelodysplastic Syndromes”
“Waldenstrom Macroglobulinemia”
“Lymphoma”
“Multiple Myeloma”
“Multiple Myeloma”
“Leukemia”
“Leukemia”
“Hematologic Neoplasms”
“Hematologic neoplasm*”
“Hematologic malignan*”
“malignant*”
“neoplasm*”
“hematologic*”
“hematologic*”
COVID-19-related keywords, MeSH terms “Vaccination”
“COVID-19 vaccines/administration and dosage”
“COVID-19 vaccines/immunology”
“SARS-COV-2 VACCINES”
“COVID-19 VACCINES”
Table 3. Population Characteristics of the Included Studies.

From: Efficacy of COVID-19 Vaccines in Patients with Hematological Malignancy Compared to Healthy Controls: A Systematic Review and Meta-analysis

Study information Population Exposure Comparison Outcome Risk of bias
First Author, Year, Country, Study design Seroconversion in patients’ group (S.R-Seroconversion rate) Hematological malignancy type Age in years, % of male Vaccine Dose interval Dose administered Comparison group, age in years, % of male Seroconversion in healthy controls (S.R-Seroconversion rate) Seroconversion cutoff value
Aleman et al., 2021, USA, Prospective cohort Dose 2: MM Mean [range]: 65 [47–79], 63% BNT162b2, mRNA-1273 28D or 21D Second Dose Healthy participants (n = 12), Mean [range]: 59 [45–64], 50% 12 ≥3.2 AU/mL 7
Patients (n = 44) (n = 12)
Seronegative (n = 27) S.R-100%
Seropositive (n = 17)
S.R-39%
Avivi et al., 2021, Israel, Prospective cohort Dose 2: MM, SM Median [range]: 70 [38–94], 56% BNT162b2, mRNA-1273 21D Second Dose Median [range]: 67 [41–84], 42.2% 63 ≥0.8 IU/mL 7
Patients (n = 171) (n = 64)
Seronegative (n = 38) S.R-98%
Seropositive (n = 133)
S.R-78%
Bergman et al., 2021, Sweden, Prospective cohort Dose 2: CLL NA BNT162b2, mRNA-1273 21D Second Dose NA 69 ≥0.8 U/mL 9
Patients (n = 388) (n = 2)
Seronegative (n = 108) S.R-95.8%
Seropositive (n = 280)
S.R-72%
Bitoun et al., 2021, France, Retrospective cohort Dose 2: MM Median [range]: 71 [46–93], 44% BNT162b2, mRNA-1273 28D Second Dose Median [range]: 58 [26–88], 28.6% 26 ≥0.4 IU/mL 5
Patients (n = 27) (n = 28)
Seronegative (n = 3) S.R-96%
Seropositive (n = 24)
S.R-89%
Canti et al., 2021, Belgium, Prospective cohort Dose 2: alloHCT Median [range]: 60 [26–76], 47.5% BNT162b2, mRNA-1273 21D Second Dose Median [range]: 48 [23–64], 27.5% 40 ≥5 IU/mL 8
Patients (n = 37) S.R-88%
Seronegative (n = 5)
Seropositive (n = 32)
S.R-86%
Chowdhury et al., 2021, UK, Retrospective cohort Dose 1: CML, ET, PV, MF, MDS Median [IQR]: 62 [52–73], 45.8% BNT162b2, AZD1222 2 W First Dose Median [range]: 62 [60–76] 224 ≥50 AU/mL 6
Patients (n = 59) (n = 232)
Seronegative (n = 25) S.R-97%
Seropositive (n = 34)
S.R-58%
Chung et al., 2021, USA, Prospective cohort Dose 1: leukemia, lymphoma, MM Median [range]: 65 [22–97], 56.4% BNT162b2, mRNA-1273 28D or 21D First Dose and Second Dose Median [range]: 31 [22–67] First Dose: 59 Immunoassay ≥50.0 AU/mL 6
Patients (n = 167) (n = 59)
Seronegative (n = 81) S.R-100%
Seropositive (n = 86) Second Dose: 54
(n = 54)
Dose 2: S.R-100%
Patients (n = 456)
Seronegative (n = 142)
Seropositive (n = 314)
S.R-51% & 69%
Crombie et al., 2021, USA, Prospective cohort Dose 1: Lymphoma and CLL Median [range]: 69 [30–82], 43.5% BNT162b2, mRNA-1273 28D or 21D First Dose and Second Dose Median [range]: 24 [22–56], 43.5% First Dose: 23 1.07 5
Patients (n = 22) Second Dose: 23
Seronegative (n = 13)
Seropositive (n = 9)
Dose 2:
Patients (n = 21)
Seronegative (n = 9)
Seropositive (n = 12)
S.R-41% & 57%
Fiorino et al., 2021, Italy, Prospective cohort Dose 2: MF Median [range]: 67 [31–85], 50% BNT162b2, mRNA-1273 3–4 W Second Dose NA 40 ≥30% 7
Patients (n = 42) (n = 40)
Seronegative (n = 10) S.R-100%
Seropositive (n = 32)
S.R-76%
Gastinne et al., 2022, France, Prospective cohort Dose 2: lymphoma, leukemia Median [range]: 62 [21–79], 60% BNT162b2 28D Second Dose NA 25 ≥0.8 U/mL 6
Patients (n = 20)
Seronegative (n = 14)
Seropositive (n = 6)
S.R-30%
Gavriatopoulou et al., 2021, Greece, Prospective cohort Dose 1: WM, CLL, NHL Median [IQR]: 75 [40–88], 48.3% BNT162b2, AZD1222 21D-3M First Dose NA 114 ≥30% = positive, ≥50% = clinically relevant inhibition) 8
Patients (n = 58) (n = 232)
Seronegative (n = 50) S.R-54%
Seropositive (n = 8)
S.R-14%
Gavriatopoulou et al., 2021, Greece, Prospective cohort Dose 1: WM Median [IQR]: 73 [64–81], 43.4% BNT162b2, AZD1222 21D-3M First Dose and Second Dose Median [IQR]: 66 [62–82], 46.2% First Dose: 212 ≥30% = positive, ≥50% = clinically relevant inhibition) 8
Patients (n = 106) Second Dose: 212
Seronegative (n = 70) S.R-96.2%
Seropositive (n = 36)
Dose 2:
Patients (n = 74)
Seronegative (n = 29)
Seropositive (n = 45)
S.R-34% & 61%
Ghione et al., 2021, USA, Prospective cohort Dose 2: lymphoma Median [range]: 70 [35–91], 52.3% BNT162b2, mRNA-1273 and Ad26.COV2.S 28D or 21D Second Dose NA 154 ≥1.0 6
Patients (n = 86) (n = 154)
Seronegative (n = 50) S.R-100%
Seropositive (n = 36)
S.R-42%
Guglielmelli et al., 2021, Italy, Prospective cohort Dose 1: MF, ET, PV NA BNT162b2, AZD1222 28D or 21D First Dose NA 14 ≥15 AU/mL 6
Patients (n = 30) (n = 14)
Seronegative (n = 12) S.R-100%
Seropositive (n = 18)
S.R-60%
Herishanu et al., 2021, Israel, Prospective cohort Dose 2: CLL Median [IQR]: 69.0 [63.0–73.7], 67.1% BNT162b2 21D Second Dose Median [IQR]: 68 [64–74.7] 52 ≥0.8 IU/mL = positive 8
Patients (n = 52) (n = 52)
Seronegative (n = 25) S.R-100%
Seropositive (n = 27)
S.R-52%
Jurgens et al., 2021, USA, Prospective cohort Dose 2: Lymphoma and CLL Median [range]: 71 [24–90], 53.7% BNT162b2, mRNA-1273 28D or 21D Second Dose NA 35 10000 5
Patients (n = 67)
Seronegative (n = 36)
Seropositive (n = 31)
S.R-46%
Lim et al., 2021, UK, Prospective cohort Dose 1: lymphoma Median [IQR]: 69 [57–74], 62.8% ChAdOx1, BNT162b2 10-12 W First Dose and Second Dose Median [IQR]: 45 [34–47], 33.3% 150 Meso scale discovery >0.55 BAU/mL, Anti–SARS-CoV-2 RBD IgG >0.73 BAU/mL 6
Patients (n = 59) (n = 150)
Seronegative (n = 27) S.R-100%
Seropositive (n = 32)
Dose 2:
Patients (n = 86)
Seronegative (n = 25)
Seropositive (n = 61)
S.R-54% & 71%
Mairhofer et al., 2021, Austria, Prospective cohort Dose 2: Cancer NA BNT162b2, mRNA-1273 28D or 21D Second Dose NA 28 ≥50 IU/mL 7
Patients (n = 45) (n = 29)
Seronegative (n = 19) S.R-96.6%
Seropositive (n = 26)
S.R-58%
Malard et al., 2021, France, Retrospective cohort Dose 2: LM, MM Median [range]: 68.9 [21.5–91.7], 59.7% BNT162b2 28D Second Dose NA ≥50 AU/mL = positive; ≥3100 = neutralization) 9
Patients (n = 196)
Seronegative (n = 105)
Seropositive (n = 91)
S.R-46%
Marasco et al., 2022, Italy, Prospective cohort Dose 2: LM Median [range]: 56 [46–62], 56.3% BNT162b2, mRNA-1273 28D or 21D Second Dose Median [range]: 56 [46–62], 56.3% 167 ≥0.8 IU/mL 9
Patients (n = 167) (n = 167)
Seronegative (n = 60) S.R-100%
Seropositive (n = 107)
S.R-64%
Marchesi et al., 2022, Italy, Prospective cohort Dose 2: MM NA BNT162b2 21D Second Dose NA 28 ≥15 U/m 6
Patients (n = 49) (n = 28)
Seronegative (n = 12) S.R-100%
Seropositive (n = 37)
S.R-76%
McKenzie et al., 2021, UK, Prospective cohort Dose 2: HM Median [IQR]: 35 [27–48], 64.7% BNT162b2, mRNA-1273 70D Second Dose Median [IQR]: 66 [52.75–73], 69.2% 22 antibody level ED50, nAb assay: IC50 5
Patients (n = 51) (n = 26)
Seronegative (n = 29) S.R-88%
Seropositive (n = 22)
S.R-43%
Monin et al., 2021, UK, Prospective cohort Dose 1: Hematological Cancer Median [IQR]: 73 [64.5–79.5], 52.3% BNT162b2 21D First Dose and Second Dose Median [IQR]: 40.5 [31.3–50], 52.9% First Dose: 32 ≥70 EC50 = positive 7
Patients (n = 44) (n = 34)
Seronegative (n = 36) S.R-94%
Seropositive (n = 8) Second Dose: 12
(n = 12)
Dose 2: S.R-100%
Patients (n = 5)
Seronegative (n = 2)
Seropositive (n = 3)
S.R-18% & 60%
Parry et al., 2022, UK, Prospective cohort Dose 2: B cell CLL Median [IQR]: 67 [60–72], 53% AZD1222, BNT162b2 3 W Second Dose Median [IQR]: 71 [64–77], 55.9% 93 ≥0.8 7
Patients (n = 500) (n = 93)
Seronegative (n = 165) S.R-100%
Seropositive (n = 335)
S.R-67%
Parry et al., 2021, UK, Prospective cohort Dose 1: CLL Median [IQR]: 69 [63–74], 54.7% AZD1222, BNT162b2 12 W and 3 W First Dose and Second Dose NA First Dose: 95 ≥0.8 7
Patients (n = 86) Second Dose: 59
Seronegative (n = 57) (N = 95 & 59)
Seropositive (n = 29) S.R-100%
Dose 2:
Patients (n = 12)
Seronegative (n = 3)
Seropositive (n = 9)
S.R-34% & 75%
Peeters et al., 2021, Belgium, Prospective multicohort Dose 2: Cancer Median [range]: 63 [25–79], 58.5% BNT162b2 21D Second Dose NA Second Dose: 40 ≥5 IU/mL 6
Patients (n = 41) (n = 40)
Seronegative (n = 29) S.R-100%
Seropositive (n = 12)
S.R-29%
Perry et al., 2021, Israel, Prospective cohort Dose 2: B-NHL Median [range]: 64 [20–92], 59.1% BNT162b2 21D Second Dose Median [range]: 66 [25–83], 44.6% 65 ≥0.8 IU/mL 8
Patients (n = 149) S.R-98.5%
Seronegative (n = 76)
Seropositive (n = 73)
S.R-49%
Pimpinelli et al., 2021, Italy, Prospective cohort Dose 1: MM, MPM Median [range]: 73 [47–78] BNT162b2, mRNA-1273 21D First Dose and Second Dose Median [range]: 81 [79–87], 50% First Dose: 36 ≥15 U/m 9
Patients (n = 92) Median [range]: 70 [28–80], 53.3% Second Dose: 36
Seronegative (n = 57) n = 36
Seropositive (n = 35) S.R-100%
Dose 2:
Patients (n = 92)
Seronegative (n = 15)
Seropositive (n = 77)
S.R-38% & 84%
Rahav et al., 2021, Israel, Prospective cohort Dose 2: CLL, NHL, MM, and MDS Median [IQR]: 69 [61–74] BNT162b2 21D Second Dose NA 269 ≥1.1 9
Patients (n = 529) Median [IQR]: 66 [59–73] (n = 272)
Seronegative (n = 175) Median [IQR]: 62 [49–70] S.R-98.9%
Seropositive (n = 354) Median [IQR]: 73 [66–80], 58.8%
S.R-67%
Schiller-Salton et al., 2021, Israel, Prospective cohort Dose 2: MM Mean ± SD: 67.8 ± 9.9, 58.50% BNT162b2 30D Second Dose NA Second Dose: 360 ≥150 AU/mL 8
Patients (n = 176)
Seronegative (n = 47)
Seropositive (n = 129)
S.R-73%
Shem-Tov et al., 2022, Israel, Prospective cohort Dose 2: HSCT Mean ± SD: 58 ± 14.0, 63.20% BNT162b2, mRNA-1273 21D Second Dose Mean ± SD: 55.6 ± 14.2, 24.3% 269 Cut point: >1.1 7
Patients (n = 152) (n = 272)
Seronegative (n = 34) S.R-98.9%
Seropositive (n = 118)
S.R-78%
Shen et al., 2021, Australia, Prospective cohort Dose 2: CLL Median [range]: 71.5 [22–94], 56.3% BNT162b2, mRNA-1273, AZD1222 2-4 W Second Dose NA 25 ≥50 AU/mL 6
Patients (n = 160)
Seronegative (n = 72)
Seropositive (n = 88)
S.R-55%
Stampfer et al., 2021, USA, Retrospective cohort Dose 1: MM Median [range]: 68 [35–88], 59.4% BNT162b2, mRNA-1273 28D or 21D First Dose and Second Dose Median [range]: 61 [26–85] First Dose: 31 50-250 IU/mL partial response, >250 IU/mL 8
Patients (n = 96) Second Dose: 31
Seronegative (n = 76) n-31
Seropositive (n = 20)
S.R-100%
Dose 2:
Patients (n = 96)
Seronegative (n = 32)
Seropositive (n = 64)
S.R-21% & 67%
Terpos et al., 2021, Greece, Prospective cohort Dose 1: CLL, NHL, HL Mean ± SD: 64.6 ± 14.3, 50% BNT162b2 21D First Dose and Second Dose Mean ± SD: 69.8 ± 12.5, 44.9% First Dose: 152 GenScript (≥30% = positive, ≥30% = clinically relevant) 6
Patients (n = 132) (n = 214)
Seronegative (n = 103) S.R-71%
Seropositive (n = 29) Second Dose: 214
(n = 214)
Dose 2: S.R-98.1%
Patients (n = 132)
Seronegative (n = 65)
Seropositive (n = 67)
S.R-22% & 51%
Terpos et al., 2021, Greece, Prospective cohort Dose 1: MM, SM, MGUS Median [IQR]: 74 [62–80], 54.7% BNT162b2, AZD1222 21D-3M First Dose and Second Dose NA First Dose: 145 GenScript (≥30% = positive, ≥30% = clinically relevant) 8
Patients (n = 276)
Seronegative (n = 159) (n = 225)
Seropositive (n = 117)
S.R-64.2%
Dose 2: Second Dose: 204
Patients (n = 276) (n = 226)
Seronegative (n = 80) S.R-90.3%
Seropositive (n = 196)
S.R-42% & 71%
Terpos et al., 2021, Greece, Prospective cohort Dose 1: MM Mean ± SD: 81.68 ± 7.63, 60.40% BNT162b2 21D First Dose Mean ± SD: 81.56 ± 8.11, 54.8% 57 GenScript (≥30% = positive, ≥30% = clinically relevant) 8
Patients (n = 48) (n = 104)
Seronegative (n = 36) S.R-54.8%
Seropositive (n = 12)
S.R-25%
Table 3. Population Characteristics of the Included Studies.

From: Efficacy of COVID-19 Vaccines in Patients with Hematological Malignancy Compared to Healthy Controls: A Systematic Review and Meta-analysis

Study information Population Exposure Comparison Outcome
First Author, Year, Country, Study design Seroconversion in patients’ group (S.R-Seroconversion rate) Hematological malignancy type Age in years, % of male Vaccine Dose interval Dose administered Comparison group, age in years, % of male Seroconversion in healthy controls (S.R-Seroconversion rate) Seroconversion cutoff value Risk of bias
Thakkar et al., 2021, USA, Retrospective cohort Dose 2: HM Median [range]: 67 [27–90], 42% BNT162b2, mRNA-1273, Ad26.COV2.S 21D or 28D Second Dose NA 26 ≥ 50 AU/mL 7
Patients (n = 66) (n = 26)
Seronegative (n = 10) S.R-100%
Seropositive (n = 56)
S.R-85%
Tzarfati et al., 2021, Israel, Prospective cohort Dose 2: HM Median [IQR]: 70 [61–78], 55.9% BNT162b2 21D Second Dose Median [IQR]: 69 [58–74], 43.5% 107 ≥12 AU/mL positive) 8
Patients (n = 315) (n = 108)
Seronegative (n = 80) S.R-99%
Seropositive (n = 235)
S.R-75%
Van Oekelen et al., 2021, USA, Retrospective cohort Dose 2: MM Median [range]: 68 [38–93], 58.1% BNT162b2, mRNA-1273 28D or 21D Second Dose NA 67 5 AU/mL 8
(n = 260) (n = 67)
Seronegative (n = 41) S.R-100%
Seropositive (n = 219)
84%
Table 4. Newcastle–Ottawa Scale for Risk of Bias Assessment of the Included Studies.

From: Efficacy of COVID-19 Vaccines in Patients with Hematological Malignancy Compared to Healthy Controls: A Systematic Review and Meta-analysis

Study Selection Comparability Outcome Overall
Representativeness of the exposed cohort Selection of the nonexposed cohort Ascertainment of exposure Outcome not present at start Assessment of outcome Adequate follow-up length Adequacy of follow up
Aleman et al., 2021 (22) * * * * * * * 7
Avivi et al., 2021 (23) * * * * * * * 7
Bergman et al., 2021 (24) * * * * ** * * * 9
Bitoun et al., 2021 (25) * * * * * 5
Canti et al., 2021 (26) * * * * * * * * 8
Chowdhury et al., 2021 (27) * * * * * * 6
Chung et al., 2021 (28) * * * * * * 6
Crombie et al., 2021 (29) * * * * * 5
Fiorino et al., 2021 (30) * * ** * * * 7
Gastinne et al., 2022 (31) * * * * * * 6
Gavriatopoulou et al., 2021 (32) * * * * * * * * 8
Gavriatopoulou et al., 2021 (33) * * * * * * * * 8
Ghione et al., 2021 (34) * * * * * * 6
Guglielmelli et al., 2021 (35) * * * * * * 6
Herishanu et al., 2021 (36) * * * ** * * * 8
Jurgens et al., 2021 (37) * * * * * 5
Lim et al., 2021 (38) * * * * * * 6
Mairhofer et al., 2021 (39) * * * * * * * 7
Malard et al., 2021 (40) * * * * ** * * * 9
Marasco et al., 2022 (41) * * * * ** * * * 9
Marchesi et al., 2022 (42) * * * * * * 6
McKenzie et al., 2021 (43) * * * * * 5
Monin et al., 2021 (44) * * * * * * * 7
Parry et al., 2022 (45) * * * * * * * 7
Parry et al., 2021 (46) * * * * * * * 7
Peeters et al., 2021 (47) * * * * * * 6
Perry et al., 2021 (48) * * * ** * * * 8
Pimpinelli et al., 2021 (49) * * * * ** * * * 9
Rahav et al., 2021 (50) * * * * ** * * * 9
Schiller-Salton et al., 2021 (51) * * * ** * * * 8
Shem-Tov et al., 2022 (52) * * ** * * * 7
Shen et al., 2021 (53) * * * * * * 6
Stampfer et al., 2021 (54) * * * ** * * * 8
Terpos et al., 2021 (55) * * * * * * * * 8
Terpos et al., 2021 (56) * * * * * * * * 8
Terpos et al., 2021 (57) * * * * * * 6
Thakkar et al., 2021 (58) * * * * * * * 7
Tzarfati et al., 2021 (8) * * * ** * * * 8
Van Oekelen et al., 2021 (59) * * * ** * * * 8
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