How to Treat Ph-Negative Precursor B-Cell ALL and Ischemic Cardiomyopathy

Anjali Advani, MD
Staff Physician in the Department of Hematologic Oncology and Blood Disorders and Director of the Inpatient Leukemia Program at the Taussig Cancer Institute at Cleveland Clinic

This month, Anjali S. Advani, MD, discusses the management of Ph-negative ALL in a patient with ischemic cardiomyopathy.

And don’t forget to check out next month’s clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!


What induction regimen would you choose for a patient with Philadelphia chromosome–negative (Ph–) precursor B-cell acute lymphocytic leukemia (ALL) and ischemic cardiomyopathy with a left ventricular ejection fraction of 35 percent?


Standard induction regimens for patients with Ph– B-cell ALL include an anthracycline. However, administration of an anthracycline may not be safe in a patient with an ejection fraction of 35 percent. One treatment option in this setting would be CVP (cyclophosphamide, vincristine, prednisone) and the addition of rituximab if the patient’s leukemia is CD20-positive. Intrathecal therapy would also be used for central nervous system (CNS) prophylaxis. CVP is used as part of the backbone of most ALL regimens, but would be less intensive and have a lower chance of achieving complete remission (CR) and minimal residual disease (MRD) negativity. If the patient had persistent morphologic disease or MRD positivity, the bispecific T-cell engaging antibody blinatumomab would then be an excellent option.

Alternative options could include a high-dose cytarabine-based regimen, FLA (fludarabine, cytarabine, granulocyte colony stimulating factor), or MOAD (methotrexate, vincristine, PEG-asparaginase, dexamethasone). These latter regimens have been used in the setting of relapsed/refractory ALL with reasonable response rates.

In this patient’s case, I would favor the first approach (CVP with or without rituximab) with intrathecal chemotherapy as CNS prophylaxis followed by blinatumomab if the patient remains refractory or is MRD positive. Unfortunately, there are no data with a curative ALL treatment regimen omitting an anthracycline and not proceeding with allogeneic hematopoietic cell transplantation (alloHCT). However, the toxicity and response rates with CVP, rituximab, and blinatumomab are the best of the various options listed. In the setting of MRD-positive disease, blinatumomab has also led to durable remissions in the absence of alloHCT.

A recent clinical trial in older patients with Ph– B-cell ALL (SWOG 1318) evaluated blinatumomab for induction and postremission therapy followed by POMP (prednisone, vincristine, 6-mercaptopurine, methotrexate) maintenance. This trial recently completed accrual and should address the outcomes of patients who are not candidates for intensive chemotherapy.

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I have a 22-year-old female patient with stage 2a lymphocyte-predominant Hodgkin lymphoma involving lymph nodes in the pelvis who presented while pregnant (she has since delivered a healthy child.). Her disease is progressing slowly, but a recent CT scan showed slightly increasing nodes, so she needs to begin therapy. The radiation oncologist does not want to treat her because of her fertility. I sent her to a fertility clinic that recommended harvesting eggs, but the patient refused and “will let God decide” if she has children. I have presented her case at our lymphoma rounds and the recommendation was for six cycles of R-CHOP rather than an ABVD regimen. What would you do? If R-CHOP is the right approach, would you add an LHRH agonist?

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