June 2026 Research Update

Across these two case reports, autoimmune hemolytic anemia (AIHA) appeared as a secondary problem in the setting of cancer, either from an underlying lymphoma or after completion of cancer treatment. The overall message is that anemia in people with cancer can have more than one cause, and in rare situations can include immune-driven red blood cell destruction. Because these are single-patient reports, they cannot show how common this is or predict who will develop it. [1] [2]

In one 67-year-old man with chronic kidney disease, testing showed AIHA along with pure red cell aplasia (a bone marrow problem where the body stops making red blood cells) in association with angioimmunoblastic T-cell lymphoma. The report described a complicated lab picture, including a positive direct antiglobulin test (DAT) and low haptoglobin, and the diagnosis was confirmed through bone marrow and lymph node testing. After red blood cell transfusions and one cycle of chemotherapy (cyclophosphamide plus prednisone), the patient had partial clinical improvement and was discharged for outpatient follow-up. [1]

In a separate report, a 73-year-old woman developed warm AIHA after completing definitive chemoradiotherapy for cervical cancer. The authors presented cervical cancer as a possible cause of secondary AIHA in this situation and noted that post-treatment anemia may be mistakenly attributed to other causes if AIHA is not considered. This report did not establish whether the AIHA was triggered by the cancer itself, the treatment, or a combination. [2]

For patients and caregivers, this set of papers mainly serves as background information: it documents that AIHA can rarely occur alongside certain cancers (including lymphoma) or after cancer treatment, and that more than one process can contribute to anemia at the same time. These reports do not provide reliable estimates of risk, do not identify clear warning signs that apply to everyone, and do not define the best approach for evaluation or treatment in broader groups. The main uncertainty is how often cancer-related AIHA occurs and what mechanisms (cancer, treatment effects, immune changes) are responsible in different people.

Across two single-patient reports, autoimmune hemolytic anemia (AIHA) appeared in people living with HIV during periods of significant illness, including severe weight loss and diarrhea, kidney problems, and (in one person) metastatic cancer and recent immune therapy exposure. [3] [4] Because these are case reports, they show what can happen but cannot tell how common these situations are or which trigger matters most.

In one man in his 30s, AIHA was identified alongside HIV disease progression after tattoo exposure, with severe diarrhea, malnutrition, and acute kidney injury; testing supported ongoing red blood cell breakdown and a positive direct antiglobulin (Coombs) test. [3] After starting antiretroviral therapy plus steroid treatment and supportive care, the report describes clinical stabilization with improved nutrition and anemia by discharge.

In a 66-year-old man with HIV and metastatic anal cancer who had recently received a PD-1 inhibitor, the report describes recurrent mixed-type AIHA with Evans syndrome (AIHA together with immune low platelets), with multiple relapses after initial steroid and intravenous immune globulin treatment. [4] Hemoglobin stabilized for a sustained period after rituximab, although platelet recovery did not track perfectly with hemoglobin changes, and the authors noted that full testing for cold-type antibodies was not done.

For patients and caregivers, these reports mainly add background on how AIHA may show up in real life when HIV and other major health issues overlap, including severe gastrointestinal symptoms, malnutrition, kidney problems, cancer, or exposure to immune-based cancer treatments. [3] [4] What remains uncertain is how often each factor contributes, which HIV-related situations carry the highest risk, and how best to fully classify AIHA subtypes in complex cases when some tests are not performed.

Across these papers, autoimmune hemolytic anemia (when the immune system attacks red blood cells) was described as an uncommon but potentially serious side effect of immune checkpoint cancer drugs. The overall pattern was that many patients improved after the immunotherapy was stopped and immune-calming medicines were used, but the timing of onset varied widely from early to delayed. [5] [6]

In a retrospective review of 29 people who developed autoimmune hemolytic anemia after nivolumab, the condition started a median of 57 days after the first dose. Most had a positive direct antiglobulin test (a blood test that can support the diagnosis), and the most common pattern was the "warm" type of autoimmune hemolytic anemia. After nivolumab was stopped and patients received steroids, other immune-suppressing medicines, and transfusion support as needed, 89.7% reached remission. [5]

Two case reports in older men with bile duct cancer described a related situation called Evans syndrome, where autoimmune hemolytic anemia happens together with low platelets. Both developed this during durvalumab maintenance therapy, and in these two individuals the problem appeared after a long delay of about 11 months on treatment. Each improved with corticosteroid therapy, and blood tests supported immune-related red cell breakdown along with platelet-targeting antibodies. [6]

For patients and caregivers, these studies add context that immune checkpoint drugs can sometimes trigger immune attacks on blood cells, including red blood cells and, in some cases, platelets. The evidence here is mainly from one moderate-sized retrospective study and two individual cases, so it cannot show how often this happens or predict who will get it. What remains uncertain is why onset timing ranges from weeks to many months, and whether certain cancer types or treatment schedules change that risk.

Across these reports, autoimmune hemolytic anemia (AIHA) appeared as part of broader immune system disorders caused by specific genetic changes, rather than as an isolated blood problem. Both papers describe children with immune dysregulation that included repeated infections and immune overgrowth (such as enlarged lymph nodes or spleen), and both highlight that similar patterns have been seen in other published cases. [7] [8]

In one report, a 10-year-old boy had an autoimmune lymphoproliferative syndrome-like condition caused by a new (de novo) STAT3 gain-of-function change, with low platelet and neutrophil (white blood cell) counts, including immune thrombocytopenia, enlarged lymph nodes and spleen, and repeated infections; AIHA was not among his reported problems. Testing showed immune-cell patterns described in other STAT3-related cases, and the child responded well to a Janus kinase (JAK) inhibitor in this single-patient report. In the authors' review of 66 earlier STAT3 cases, immune thrombocytopenia was the most common blood-count problem and was often accompanied by AIHA. [7]

In a second report, a 5-year-old boy with biallelic RASGRP1 deficiency had severe large-vessel blood vessel disease, secondary antiphospholipid syndrome (a clotting-related autoimmune condition), and life-threatening AIHA that was ultimately fatal despite multiple therapies. The authors literature review of 14 earlier cases reported frequent infections and immune overgrowth/autoimmunity, and noted that some patients who received a stem cell transplant were reported to go into remission in those case reports. [8]

For patients and caregivers, these papers mainly add background context: in some children, AIHA can be one sign of a rare inherited or new genetic immune disorder, especially when there are repeated infections, enlarged lymph nodes or spleen, other autoimmune blood count problems, or unusual issues like blood clots or blood vessel inflammation. The evidence here comes from individual case reports plus small literature reviews, so it cannot show how often these conditions occur or predict outcomes for any one person. What remains uncertain is which patients with AIHA are most likely to have an underlying genetic immune disorder and how consistently different treatment approaches work across larger groups.

Across these papers, hemolysis was described in a few different settings where immune reactions can overlap: after red blood cell transfusion, during pregnancy in people needing repeated transfusions, and after intravenous immune globulin (IVIG). A recurring message was that similar symptoms and lab changes can have different causes (such as transfusion-related antibodies versus autoimmune hemolytic anemia), and the right blood bank tests helped clarify what was happening in these reports. [9] [10] [11]

In one adult case, a delayed hemolytic transfusion reaction due to an anti-Jka antibody occurred alongside warm autoimmune hemolytic anemia, creating a diagnostic challenge. The patient improved quickly after corticosteroid treatment and receiving red blood cells that lacked the triggering antigen, and the authors highlighted that more advanced blood testing may be needed when routine tests miss short-lived antibodies. [9]

In a small pregnancy case series in thalassemia, the authors described transfusion refractoriness (less improvement than expected after transfusion) as an early warning sign of an immune hemolytic crisis. They emphasized doing an irregular antibody screen and a direct antiglobulin test (DAT, sometimes called a Coombs test) at the same time to help separate alloimmune hemolysis from autoimmune hemolytic anemia; outcomes varied across the three cases, including one maternal death from postpartum sepsis. [10]

In four children treated with IVIG for Kawasaki disease, hemolysis developed within days and DAT testing became positive after the infusion. Two children needed transfusion, but all recovered with supportive care (iron and folate) and none needed corticosteroids in this small series; the authors noted all were non-O blood types, consistent with passive transfer of anti-A or anti-B antibodies in IVIG as a possible explanation. [11]

One lab and animal study explored a different angle: altering donor red blood cells to mask their surface markers using a polysialic acid shield. In mouse models of autoimmune hemolytic anemia and in lab testing, these modified cells showed less antibody binding, less uptake by immune cells, and longer circulation time, with reported biocompatibility in an allogeneic transfusion setting. [12]

For patients and caregivers, this group of papers mainly adds background on why hemolysis can sometimes appear around transfusions or IVIG, and why it may not be immediately clear whether the cause is a transfusion reaction, autoimmune hemolytic anemia, or both. The clinical reports are small (single cases or very small series), so they cannot estimate how often these problems occur, but they show real-world situations where timing (hours to days) and targeted blood testing changed how the hemolysis was understood. The red blood cell masking approach is early, preclinical research in mice and lab models, so it is not ready for routine care and its safety and effectiveness in people remain uncertain. [9] [10] [11] [12]

Across these papers, the clearest clinical signal was that some people with warm autoimmune hemolytic anemia (AIHA) or Evans syndrome may be able to control hemolysis while reducing reliance on corticosteroids, but the strength of evidence varies. One prospective single-center trial reported high and fairly durable response rates with sirolimus, while two individual case reports described successful outcomes with efgartigimod (after limited responses to other therapies) and with early rituximab plus steroids after organ transplant. [13] [14] [15]

In a prospective, open-label, single-arm study of 78 adults with relapsed or refractory warm AIHA or Evans syndrome, sirolimus led to responses in about 4 out of 5 patients by 6 months, with similar results at 12 months. Side effects were reported in 28.2% of participants and were described as mostly mild and reversible, and relapse occurred in 12.7%. [13]

One case report of an 80-year-old man with Evans syndrome described efgartigimod being used as a steroid-sparing approach after limited response to rituximab and corticosteroids. Platelet counts improved, hemolysis stabilized, and corticosteroids were tapered without relapse, although the report also noted steroid-related delirium that required dose reduction. Because this is a single patient, it cannot show how often this would happen in others. [14]

Another case report described a 30-year-old woman who developed warm AIHA many years after a liver transplant while taking tacrolimus. She reached complete remission with high-dose steroids and early rituximab, and her tacrolimus was only modestly reduced rather than stopped, with no transfusion reaction reported when compatible blood was given. As a one-patient report, it mainly illustrates what may be possible in a very specific context rather than setting expectations for most patients. [15]

For patients and caregivers, this set of studies adds context to ongoing efforts to limit long-term corticosteroid exposure in warm AIHA and Evans syndrome. Sirolimus has moderate-strength evidence from a single-arm trial suggesting many participants improved over months, while efgartigimod and early rituximab are supported here only by individual case reports in particular situations (Evans syndrome after limited response to other treatments, and AIHA after liver transplant). What remains uncertain is how these options compare with each other or with other standard treatments, and which patient features best predict benefit, because the trial did not identify baseline predictors and the case reports cannot be generalized. [13] [14] [15]

This translational study focused on why glucocorticoids (steroids) can increase red blood cell production in autoimmune hemolytic anemia (AIHA), beyond their immune-suppressing effects. Using AIHA patient samples along with animal and lab models, the authors reported that steroid-driven red blood cell production depended on CD163-positive macrophages in the bone marrow and on coordinated handling of iron within structures that support developing red cells. [16]

In the animal models, steroid-induced red blood cell production was much weaker when CD163 was missing, and this was linked to disrupted bone marrow "niches" for developing red cells and problems with iron metabolism. The study also reported that steroid treatment restored iron metabolism and reduced inflammatory responses in bone marrow CD163-positive macrophages, pointing to a CD163-erythroblastic island axis as a potential future therapeutic target. [16]

For patients, this paper mainly provides background on possible biological reasons steroids can help some people recover red blood cells in AIHA, even though steroids also carry side effects. The work is preclinical (lab and animal models, plus human samples) and does not test a new treatment in patients, so it is not evidence that targeting CD163 is ready for routine care. The uncertainty is how well this pathway will translate into safe, effective steroid-sparing treatments in real-world AIHA. [16]

Across these papers, the main message was that autoimmune hemolytic anemia (AIHA) is not one single condition: warm, cold, and mixed types can look similar day to day but differ on blood testing, and that difference can point to an underlying trigger that also needs attention. The evidence here is exploratory and based mostly on a small case series and individual case reports, so it describes what happened in specific patients rather than predicting what will happen for everyone. [17] [18]

In a case series of three women, subtype-focused testing (including the direct antiglobulin test, also called DAT, with more specific follow-up testing) was used to classify cold, warm, and mixed AIHA, alongside common hemolysis labs such as bilirubin and lactate dehydrogenase and review of the blood smear. One patient with cold AIHA was found to have an underlying B-cell acute lymphoblastic leukemia, and she improved after both AIHA-directed care and leukemia-directed chemotherapy; the warm and mixed cases also improved with supportive care and steroids-based treatment. [17]

A separate case report highlighted diagnostic complexity when AIHA appears in an older adult with other immune blood problems. An 82-year-old man with long-standing immune thrombocytopenia (ITP) developed warm AIHA with an IgG-positive DAT and C3d-negative testing, and a bone marrow biopsy did not show a blood cancer, helping narrow the cause. His hemoglobin improved after high-dose corticosteroids, and he needed fewer transfusions afterward. [18]

For patients and caregivers, this set of papers is mainly background that explains why clinicians often spend time confirming the AIHA type and looking for related conditions, because those details can change how the situation is interpreted. These reports do not show that any one testing approach or treatment plan is best for everyone; they show how subtype testing and broader evaluation helped in a few real-world cases. What remains uncertain is how often these patterns apply across larger, more diverse groups of people with AIHA. [17] [18]

Two papers focused on less common and less predictable issues around autoimmune hemolytic anemia (AIHA): a rare neurologic complication described in a single patient, and a possible blood-based marker for therapy-related AIHA in people with chronic lymphocytic leukemia. Both are early signals rather than firm conclusions because one is a case report and the other is a retrospective study that the authors say needs validation. [19] [20]

In one case report, a 51-year-old woman with AIHA developed reversible cerebral vasoconstriction syndrome (RCVS), with acute, temporary neurologic symptoms and severe headache. Brain vessel imaging (magnetic resonance angiography) showed multifocal segmental narrowing that improved on follow-up without a specific RCVS-directed intervention described. The authors suggested active hemolysis, red blood cell transfusion, and corticosteroid therapy as possible contributing factors in this situation. [19]

In a retrospective study of people with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide, baseline SLC28A3 gene expression was about sevenfold lower in those who later developed AIHA during or after that therapy. The study did not find a meaningful link between SLC28A3 expression and time to first treatment or overall survival in this dataset. The authors emphasized the need to confirm this in larger prospective cohorts before it could be considered reliable. [20]

For most people, these papers are most useful for understanding the range of complications that have been reported and the kinds of research questions being explored in higher-risk settings (such as chemotherapy for chronic lymphocytic leukemia). The RCVS report shows a possible, uncommon neurologic event that improved over time in one person, but it cannot estimate how often this happens. The gene-expression study suggests a potential future tool for identifying risk of therapy-emergent AIHA, but it is not yet validated for routine care. [19] [20]