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Relapsed and Refractory

Some patients have residual leukemia cells in their bone marrow even after they receive intensive treatment. In these cases, the disease is referred to as being “refractory” (or “refractory ALL”).

Other patients achieve remission but later have decreased numbers of normal blood cells and a return of leukemia cells in their bone marrow. This is referred to as a “relapse” of the disease (or “relapsed ALL”).

Ph-Negative ALL

For patients with relapsed or refractory Ph-negative ALL, there are several treatment options. One option is to use different drugs than those used during the patient’s induction regimen. These options, suggested by the NCCN guidelines, may include:

  • Blinatumomab (Blincyto®) 
  • Inotuzumab ozogamicin (Besponsa®)
  • Tisagenlecleucel (Kymriah®)
  • Combination regimens that include several chemotherapy drugs, some of which may have been given in the past. Examples of such include
    • Inotuzumab ozogamicin + mini-hyper CVD (cyclophosphamide, dexamethasone, vincristine, methotrexate, cytarabine) for patients with B-cell ALL
    • Augmented hyper-CVAD: hyperfractionated cyclophosphamide, intensified vincristine, doxorubicin, intensified dexamethasone and pegaspargase, alternating with high-dose methotrexate and cytarabine
    • MOpAD: methotrexate, vincristine, pegaspargase, and dexamethasone with rituximab for CD20-positive disease
  • Nelarabine, alone or in combination with other drugs (e.g., nelarabine, etoposide, cyclophosphamide)
  • Clofarabine, alone or in combination with other drugs (e.g., clofarabine, cyclophosphamide, etoposide)
  • Vincristine sulfate liposome (Marqibo®) 
  • Fludarabine-based regimens
    • FLAG-IDA: fludarabine, cytarabine, granulocyte colony-stimulating factor ± idarubicin
    • FLAM: fludarabine, cytarabine and mitoxantrone
  • Cytarabine-containing regimens (e.g., high-dose cytarabine, idarubicin, intrathecal methotrexate)
  • Alkylator combination regimens (e.g., etoposide, ifosfamide, mitoxantrone)
  • Brexucabtagene autoleucel (Tecartus®) 

Ph-Positive ALL

For patients with relapsed or refractory Ph+ ALL, there are several treatment options.

A patient may receive a different tyrosine kinase inhibitors (TKI). Many Ph+ ALL patients receive imatinib (Gleevec®) during induction therapy. For those patients whose disease has relapsed dasatinib (Sprycel®) or ponatinib (Iclusig®) may be treatment options.

The TKI may be given alone or combined with other drugs.  If ALL does not respond to treatment with TKIs, doctors may recommend regimens for relapsed or refractory Ph-negative ALL. These include

  • Blinatumomab
  • Inotuzumab ozogamicin
  • Tisagenlecleucel
  • Brexucabtagene autoleucel (Tecartus®) 

An an allogeneic stem cell transplantation or clinical trial may also be an option.

For information about the drugs listed on this page, visit Drug Listings.


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