Activity Faculty Scott C. Howard, MD, - PowerPoint Presentation

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Activity Faculty

Scott C. Howard, MD,

MScUniversity of Tennessee College of Health SciencesMemphis, TN

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Learning Objectives

Upon completion, participants should be able to:

Review treatment regimens for patients with relapsed ALLOptimize supportive care for patients who receive relapsed ALL therapy

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Key Considerations in the

Management of Relapsed ALL

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ALL

The incidence of ALL is highest among children and decreases with advancing age

Most common form of leukemia in childhoodOnly one-fifth of leukemia cases in adultsRoughly 80% of patients treated with risk-adapted therapy at diagnosis are cured

However, outcomes for patients with relapsed disease are poor

PRACTICE PEARL

Relapsed ALL (except for late extramedullary relapse) has a poor prognosisSlide6

When to Suspect Relapsed ALL

In general, relapse should be suspected in patients with any of the following:

New neurologic deficitsTesticular massCytopenias of unexpectedly long duration and severity during therapyBlasts noted on the peripheral blood smear or in the CSF

It is essential to confirm relapse before initiating salvage therapy

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Initial Steps for Patients With

Suspected Relapsed ALL

Confirmation of the relapse is essentialFlow cytometryPCR assays

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Initial Steps for Patients With

Suspected Relapsed ALL (cont.)

Identify site(s) of relapseBone marrow (isolated vs. combined)CNSTestesOther extramedullary sites

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Factors Affecting Risk Stratification

in Relapsed ALL

Time to relapseSite of relapseImmunophenotypeResponse to initial therapy for relapse (ie, MRD after 2 blocks)

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Defining Risk-Based Groups for Reinduction Therapy

Standard-risk treatment group: HSCT not necessary

Late relapse (≥ 36 months from initial diagnosis), ANDB-lineage ALL,

ANDMRD ≤ 0.01% after 2 blocks of induction therapy

High-risk treatment group: HSCT if possible

Early relapse (< 36 months from initial diagnosis),

OR

T-lineage ALL,

OR

MRD > 0.01% after 2 blocks of induction therapy

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Reinduction

Therapy for

Standard Risk Relapsed ALL*Regimens usually include high-dose methotrexate and high-dose cytarabine.

PRACTICE PEARL

All known-effective agents should be used at

first relapse to get the patient into a deep remission before transplant or continuation

Intensive chemotherapy with radiation in some cases

Late isolated

non-CNS

extramedullary

relapse (

eg

, testicular)

Intense relapsed induction chemotherapy regimen* followed by consolidation and continuation

Bone marrow

relapse

Intense systemic

and intrathecal chemotherapy* with cranial (or craniospinal) radiation

Late isolated

CNS relapseSlide12

Reinduction Therapy for High-Risk Relapsed ALL

Standard reinduction regimens are not sufficient for patients with high-risk relapsed ALL

PRACTICE PEARL

All known-effective agents should be used at

first relapse to get the patient into a deep remission before transplant or continuationSlide13

Investigation Into Novel Reinduction Regimens Is Ongoing

Current phase 2 study at St. Jude Children’s Research Hospital (NCT01700946)

Examining new approaches to achieve deep remission as early as possible following relapseStratifying patients into risk groups to define treatment approach

Chemotherapy for standard riskChemotherapy followed by HSCT for high risk

PRACTICE PEARL

All known-effective agents should be used at

first relapse to get the patient into a deep remission before transplant or continuationSlide14

Reinduction Therapy for High-Risk Relapsed ALL (cont.)

Once CR2 is achieved, initiate intensive chemotherapy followed by HSCT as soon as MRD-negative status is achieved

Recommend HSCT to those with high-risk featuresHSCT may be appropriate for some intermediate-risk patients in CR2

If no stem cell donor is available, proceed to consolidation and continuation therapy, as is done for standard-risk ALL

PRACTICE PEARL

All known-effective agents should be used at

first relapse to get the patient into a deep remission before transplant or continuationSlide15

Relapsed ALL Treatment Algorithm

Marrow not involved

Marrow involved

Enroll in a clinical trial

Early relapse or

T-lineage ALL or

MRD > 0.01% after initial therapy

Late relapse and

B-lineage ALL and

MRD ≤ 0.01% after initial therapy

Standard risk

MRD measurement

Suspect relapse

(New neurologic deficit, blasts on blood smear or

in CSF, prolonged cytopenias during therapy)

Confirm relapse and identify sites of disease

(BMA; neurologic, testicular, and CSF examinations)

Regimen for isolated extra-medullary relapse

Risk stratify

High risk

Induction Block II

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Relapsed ALL Treatment Algorithm

SCT

Continuation

MRD

≤ 0.01%

MRD

> 0.01%

MRD improved

No

SCT donor

MRD worse

Consider palliative care

Consider experimental therapy

Consolidation I

Consolidation I

Consolidation II

Intense block of chemotherapy

Standard risk

High riskSlide17

Preventing Toxic Death

in Relapsed ALL

Management of febrile neutropeniaEmpiric antimicrobial therapyInpatient admission

Antifungal prophylaxis Consider for all patients receiving chemotherapy

Administer until at least day 75 following

allogenic

HSCT

Avoid

antifungals

that inhibit

cytochrome

P450 3A4

isozyme

PRACTICE PEARL

Great supportive care is as important to

optimal patient outcomes as chemotherapySlide18

Key Considerations in the

Management of Relapsed ALL

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Thank You!

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