You Make the Call: Would you recommend alloHCT in a 41-year-old patient with aggressive Burkitt leukemia and ALS?

Mark Fesler, MD

Malignant Hematology Specialist
St. Luke’s Center for Cancer Care
Chesterfield, MO

CLINICAL DILEMMA

We are treating a 41-year-old male with Burkitt leukemia who had a very aggressive presentation that included pancytopenia, substantial bone marrow infiltration, tumor lysis syndrome, high fever, and bulky lymphadenopathy. He received a course of R-CODOX-M (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate) and a course of R-IVAC (rituximab, ifosfamide, etoposide, cytarabine) and was in a complete remission. Now, he is receiving his next course of R-CODOX-M, and we are planning for a final course with R-IVAC. Normally, treatment would be complete at that point. However, this patient also has autoimmune lymphoproliferative syndrome (ALPS), and we are concerned he has a high risk of relapse, both because of this underlying immune deficiency and the very aggressive presentation of his leukemia. Do you think that this is an indication for allogeneic hematopoietic cell transplantation (alloHCT)?

EXPERT OPINION

The median age for a diagnosis of the sporadic form of Burkitt lymphoma or leukemia is 45, which is close to the age of this patient.¹ The very aggressive presentation is one of the hallmarks of Burkitt lymphoma or leukemia, with a Ki67 index of nearly 100% in most cases due to the translocation of c-Myc.¹ In this case, both the patient’s age and presentation do not suggest an unusual appearance of non-Hodgkin lymphoma. While bone marrow infiltration is considered an adverse baseline prognostic factor in Burkitt lymphoma,² most patients with this diagnosis are cured with an intensive chemotherapy backbone such as hyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone), CODOX/IVAC, or dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) with rituximab immunotherapy.¹

I would need more details of how the diagnosis of autoimmune lymphoproliferative syndrome (ALPS) was made, as there are no clinical or laboratory details raising suspicion for it. There are published diagnostic criteria for ALPS,³ which include two required criteria along with multiple primary and secondary accessory criteria. The required criteria are:

• the presence of chronic (longer than six months), non-infectious, and non-malignant lymphadenopathy, splenomegaly, or both
• an elevated relative or absolute number of CD3⁺ TCR alpha beta⁺ CD4^- CD8^- T cells in the setting of normal or elevated lymphocyte count

The patient did not have a diagnosis of a non-Hodgkin lymphoma until age 41, which suggests that the presence of ALPS should be questioned. If the patient meets the diagnostic criteria for ALPS, it is likely that he is heterozygous rather than homozygous or compound heterozygote given the clinical features, with the attendant risk of a subsequent non-Hodgkin lymphoma being lower. Given the morbidity and mortality associated with allogeneic hematopoietic cell transplant (alloHCT), which has a transplant related mortality of 5% to 35%, this procedure should only be indicated if a complete remission is achieved with a chemosensitive relapse of the Burkitt lymphoma or if the patient develops another type of non-Hodgkin lymphoma. In those instances, second line therapy would be limited in curative potential with consideration of cumulative anthracycline exposure, and alloHCT would address the underlying immune defect associated with ALPS.

References:

1. Linch DC. Burkitt lymphoma in adults.Br J Haematol. 2012;156(6):693-703. 
2. Roschewski M, Dunleavy K, Abramson JS, et al. Multicenter Study of Risk-Adapted Therapy with Dose-Adjusted EPOCH-R in Adults with Untreated Burkitt Lymphoma. J Clin Oncol. 2020; 38(22):2519-2529.
3. Oliveira JB, Bleesing JJ, Dianzani U, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010;116(14):e35-e40.

NEXT MONTH'S CLINICAL DILEMMA

A 74-year-old female developed a right subsegmental pulmonary embolism (PE) three months after receiving the COVID-19 vaccine. No deep vein thrombosis (DVT) was seen on ultrasound. She was started on apixaban and underwent a work-up, which was notable for elevated anti-cardiolipin antibody titers (IgG, range 70-80 units), but normal anti-β2 glycoprotein-I antibody titers. The anti-cardiolipin antibody titers were elevated on three separate occasions, 12 weeks apart. The patient did not have a prior history of thrombosis.

She has now had more than six months of anticoagulation with apixaban. She has excellent performance status and no significant comorbidities. Based on lab criteria, she meets the Sapporo classification for antiphospholipid syndrome (APS), but clinically and demographically her case is not consistent with diagnosis. Would you stop anticoagulation, drop to prophylactic doses, or continue full dose?

How would you respond? Email us at [email protected].

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