Analysis Finds Clinical Insights for Treating AIHA, Non-Hodgkin Lymphoma

Though rare, patients with both autoimmune hemolytic anemia (AHIA) and non-Hodgkin lymphoma face stark odds of long-term survival. A new study lends insights into how to best diagnose and treat those patients.

Autoimmune hemolytic anemia (AIHA) is a disorder of hyperfunctioning B lymphocytes that sometimes accompanies lymphoma as well as other lymphatic proliferation and immune-related diseases.

About 1 in 5 patients with AIHA will also develop lymphoma, and 7-10% of people with lymphoma also have AIHA. It’s rare for a patient to have both AIHA and non-Hodgkin lymphoma (NHL). Yet, patients with both conditions face lower survival rates than patients with NHL but not AIHA.

In order to better understand the links between AIHA and NHL, a team from the First Affiliated Hospital of Guangxi Medical University, in China, decided to perform a retrospective analysis of 20 patients who had both AIHA and NHL. Their findings are reported this month in the journal Medicine.

The study included 20 patients who were treated at the hospital between 2009 and 2018. Patients were identified as having AIHA based on anemia, elevated reticulocyte count, high levels of indirect bilirubin, and positive direct antihuman globulin tests. NHL was diagnosed by bone marrow smears (BMS), bone marrow biopsy, or lymph node biopsy.

Less than 1% (0.91%) of NHL patients presented with AIHA, and just under 10% (9.8%) of AIHA patients presented with NHL.

The authors noted that AIHA was most frequently co-occurring with angioimmunoblastic T-cell lymphoma (7.31%), marginal zone B-cell lymphoma (6.25%), B-cell lymphoma-unclassified (4.25%), chronic lymphocytic leukemia/small lymphocyte lymphoma (2.5%), and mantle cell lymphoma (2.3%).

One finding that particularly surprised corresponding author Zhou Ji-Cheng, MD, was the number of AIHA/NHL patients with lymphoma bone marrow infiltration (LBMI).

“I was indeed surprised by some of the data in our cohort, including the incidence of LBMI in non-CLL (chronic lymphocytic leukemia) patients as high as 66.7%, and LBMI was detected only in 1 of BMS and [bone marrow biopsy],” Zhou told The American Journal of Managed Care® via email.

The study found patients with both AIHA and NHL had a 1-year survival rate of 70%, 3-year survival rates of 30%, and 5-year survival rates of 20%.

One of the takeaways from the study is that performing BMS or BMB alone to check for bone marrow infiltration might be insufficient. Zhou and colleagues noted that those two tests or PET/CT scans are typically used to diagnose LBMI. A limited number of patients in the hospital’s cohort underwent PET/CT, so the authors did not draw conclusions about PET/CT. However, in examining the diagnostic value of BMB or BMS alone, Zhou and colleagues found inconsistent results.

“This strongly suggests that the distribution of NHL lesions in AIHA/NHL patients is uneven, and BMB or BMS alone would result in a relatively higher missed diagnosis rate,” they write.

Thus, they suggest that in the absence of a positron emission tomography/computed tomography scan, (PET/CT), BMB and BMS ought to performed simultaneously to minimize the chance of missing LBMI. Zhou’s hospital already routinely performs both tests when diagnosing NHL, particularly in cases where diagnoses was difficult.

“This is mainly based on the experience that only BMS or [BMB] would miss the diagnosis of LBMI or even lymphoma,” Zhou said. “When we perform these two operations, we usually do MBS first, and then do a [BMB] 0.5 cm away from BMS. We feel that the above methods may increase the patient's pain, but this is unavoidable to reduce the missed diagnosis of LBMI or even lymphoma.”

As for treatment of AIHA/NHL, Zhou and colleagues say treatment generally depends on which is diagnosed first. If the two are diagnosed simultaneously, NHL treatment of chemotherapy and surgery will typically control progression of both. However, they note that ultimately, given the prognosis for these patients, current treatments are unsatisfactory.


Zhou Jc, Wu Mq, Peng Zm, Zhao Wh, Bai Zj. Clinical analysis of 20 patients with non-Hodgkin lymphoma and autoimmune hemolytic anemia: a retrospective study. Medicine. 2020;99:7(e19015).

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