Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. CLL
1.2. Autoimmunity
1.3. CLL and Dysregulation
2. CLL and AIHA
2.1. Pathogenesis of AIHA
2.2. Drugs Associated with CLL-AIHA
2.3. Diagnosis of CLL-AIHA
2.4. Main Experiences of CLL-AIHA
3. Treatment
3.1. Warm AIHA
3.1.1. Warm AIHA First Line Treatment
3.1.2. Warm AIHA Second Line Treatment
3.1.3. Warm AIHA Treatment for Refractory Cases
3.2. Cold AIHA
3.3. Supportive Management
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study Type | N of CLL Patients | No. of AIHA | AIHA Type (Cold vs. Warm) | Main Findings | References |
---|---|---|---|---|---|
Single center, retrospective | 1203 | 52 | Warm 87% Cold 13% | Lymphocyte count more than 60 × 109/L, age > 65 years, and male gender are associated to increased rate of AIHA at CLL diagnosis IgG AIHA and concomitant diagnosis of AIHA and CLL are associated to better survival | Mauro, FR et al. 2000 [31] |
Multicentric, prospective + retrospective | 3150 | 129 | Warm 89% Cold 11% | Age > 69 years, stage C, and R/R CLL are associated to AIC: | Barcellini, W. et al. 2006 [32] |
Single center, retrospective | 964 | 55 | nk | Activated lymphocyte morphology, high levels of IgG and beta-2-microglobulin, and increased expression of CD38 and/or FMC7 are related with autoimmune complications | Duek, A. et al. 2006 [33] |
Single center, retrospective | 1737 | 41 | nk | 55% Treatment naïve CLL develop autoimmune diseases | Zent, C.S. et al. 2009 [34] |
Single center, retrospective | 960 | 49 | nk | High lymphocyte count, short LDT, high serum B2M level, high ZAP-70 and CD38 expression are associated with AIC | Moreno et al. 2010 [35] |
Multicentric, retrospective | 1477 | 80 | nk | Concomitant diagnosis of AIHA andCLL diagnosis is associated with shorter survival. The presence of positive antiglobulin test even without hemolysis was associated with worse outcome. Laboratory or clinical evidence of AIHA had a significant negative impact on the survival of patients with CLL. | Shvidel, L, et al. 2013 [36] |
Single-centre prospective study | 192 | 8 (4.2%) | nk | Older age and advanced stage of CLL are associated with AICs are. | Demir C. et al 2017 [37] |
Multicentric, retrospective study | 235 | 6 (2.6%) | Neg: n = 2 Warm: n = 2 Coombs positive, not known type = 2 | Aggressive disease, poor prognostic features,, previous autoimmune phenomena or fludarabine front-line therapy are related with AIHA. BR is safe in previous AIHA orpositive DAT CLL patients. | Laurenti L. et al 2015 [25] |
Single-centre retrospective study | 795 | 27 (3.4%) | nk | Female gender, advanced stage disease, previous treatment, 11q deletion by FISH, CD38 positive and CAD are associated with autoimmune disease | Visentin A. et al 2017 [8] |
Observational retrospective study | 101 | 7 (6.9%) | nk | Patients with autoimmune cytopenia have less CLL BM infiltration and lesser response to treatment | Atef B. et al 2019 [38] |
Critical review | The commonest AIC correlating with advanced disease and high biologic risk (del 11q, del17p, unmutated IGHV) | Visco C. et al. 2014 [39] |
Warm Autoimmune Hemolytic Anemia Waiha | References |
---|---|
First line | |
Steroids (prednisone 1 mg/kg/day for 3–4 weeks; alternative dexamethasone 40 mg/day for 4 days, 2–6 cycles every 2–4 weeks) | [40,46,47,48] |
Second line | |
Rituximab 375 mg/m2 weekly × 4 weeks | [49,50] |
New targeted drugs | |
BTK inhibitors: ibrutinib and acalabrutinib | [51,52,53,54,55] |
PI3K inhibitors: idelalisib | [56] |
anti BCL2: venetoclax | [57,58] |
Chemoimmunotherapic regimens: | |
rituximab, cyclophosphamide and dexamethasone (RCD), | [59,60] |
rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) | [61] |
bendamustine and rituximab (BR) | [28] |
Third or following line | |
Alemtuzumab 30 mg × 3/week × 4–12 weeks | [51,62] |
Cytotoxic immunesuppressors, such as cyclophosphamide, azathioprine, cyclosporine and mycophenolate | [63] |
New-generation monoclonal antibodies: ofatumumab and obinutuzumab | [52] |
Cold Autoimmune Hemolytic Anemia Caiha | References |
---|---|
First line | |
Rituximab 375 mg/m2 weekly × 4 | [50,53] |
Second line | |
Rituximab plus Bendamustine 90 mg/m2 | [54] |
Rituximab plus Fludarabine 40 mg/m2 | [55] |
BTK inhibitors: ibrutinib and acalabrutinib | [64] |
Upstream complement inhibition: eculizumab | [65,66] |
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Autore, F.; Pasquale, R.; Innocenti, I.; Fresa, A.; Sora’, F.; Laurenti, L. Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review. Cancers 2021, 13, 5804. https://doi.org/10.3390/cancers13225804
Autore F, Pasquale R, Innocenti I, Fresa A, Sora’ F, Laurenti L. Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review. Cancers. 2021; 13(22):5804. https://doi.org/10.3390/cancers13225804
Chicago/Turabian StyleAutore, Francesco, Raffaella Pasquale, Idanna Innocenti, Alberto Fresa, Federica Sora’, and Luca Laurenti. 2021. "Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review" Cancers 13, no. 22: 5804. https://doi.org/10.3390/cancers13225804