Leukemia – Acute Lymphoblastic (ALL)

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ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

OVERVIEW & DEFINITIONS

What is ALL?
- Clonal overproduction of immature lymphocytes (lymphoblasts)
- B-cell ALL (B-ALL): ~75–85% of cases
- T-cell ALL (T-ALL): ~15–25% of cases
- Primary treatment goal = cure
- Treatment duration: approximately 2–3 years

Four Key Treatment Phases (in order):
1. Induction (4–6 weeks)
2. CNS Prophylaxis
3. Consolidation (20–30 weeks)
4. Maintenance (2+ years)

- CNS is a sanctuary site — intrathecal (IT) chemotherapy is mandatory for ALL patients
- Maintenance backbone: oral 6-mercaptopurine + weekly methotrexate

RISK STRATIFICATION

Poor Prognostic Factors:

- Ph+ ALL — t(9;22) → BCR-ABL1 fusion [MOST IMPORTANT poor prognostic cytogenetic finding; ~25% of adults] - Age >35
- High WBC at diagnosis
- Hypodiploidy, KMT2A rearrangement
- Persistent MRD after induction [STRONGEST overall prognostic factor]

Favorable Factors:

- Hyperdiploidy
- ETV6-RUNX1 t(12;21) — common in children

INDUCTION REGIMEN SELECTION BY PATIENT PROFILE

Patient Profile --> Preferred Regimen

Fit adult, Ph+ ALL, any age --> HyperCVAD + TKI (dasatinib or ponatinib)
Young adult/AYA, Ph− ALL --> CALGB 10403 (pediatric-inspired)
Adults 30–70, Ph− ALL --> ECOG1910 (HyperCVAD + blinatumomab) — NCCN preferred; improves OS
Older adults, Ph+ ALL --> Mini-CVD + ponatinib
Ph− B-ALL, relapsed <3 months --> Blinatumomab

Key Rules:
- CALGB 10403 and CALGB 9511: NOT for Ph+ ALL (TKI required)
- Dasatinib is the preferred TKI when CNS involvement is suspected — crosses the BBB
- TKI must be added throughout ALL phases of Ph+ ALL treatment (induction, consolidation, maintenance)
- Mini-CVD + inotuzumab + ponatinib: insufficient safety data to support this combination

INDUCTION — DRUG ROLES

- Induction backbone: prednisone/prednisolone + vincristine + daunorubicin + asparaginase
- CR backbone = vincristine + corticosteroid + anthracycline
- ASPARAGINASE DOES NOT AFFECT CR RATE — it improves leukemia-free survival (LFS) only
- Prednisolone response on day 8 is used for risk stratification

TARGETED & IMMUNOTHERAPY AGENTS

BLINATUMOMAB (CD19-directed BiTE antibody)

- Indications:
* MRD-positive disease after >= 3 blocks of intensive chemotherapy (BLAST trial criteria)
* Relapsed/refractory Ph− B-ALL
* ECOG1910 addition for Ph− adults (improves OS)
- NOT used as initial induction for a fit patient — premature after only one induction cycle
- Toxicities: CRS and ICANS (neurotoxicity)

INOTUZUMAB OZOGAMICIN (CD22-directed)

- Reserved for FULMINANT relapsed/refractory B-ALL ONLY
- NOT indicated for early post-induction MRD positivity
- Associated with sinusoidal obstruction syndrome (SOS)

NELARABINE

- Indicated for T-ALL ONLY — inappropriate for B-ALL

CAR-T CELL THERAPY

- Tisagenlecleucel (CD19): approved for patients up to age 25 with relapsed/refractory B-ALL
- Brexucabtagene autoleucel: for relapsed/refractory adult B-ALL
- Levetiracetam 500–750 mg PO/IV q12h: mandatory seizure prophylaxis starting on day of infusion; continue >= 30 days
- AVOID corticosteroids prophylactically — may impair CAR-T cell expansion; reserved for emergent toxicities

CLOFARABINE

- Reserved for pediatric patients or heavily pre-treated adult relapsed/refractory settings

TOXICITY MANAGEMENT

CYTOKINE RELEASE SYNDROME (CRS) — Blinatumomab / CAR-T

Symptoms: fever, rigors, emesis, hypotension, elevated LFTs
High disease burden = major risk factor for CRS

Grade 1 --> Supportive care only (fluids, empiric antibiotics if febrile)
Grade 2+ or Grade 1 persisting >3 days --> Tocilizumab
Grade 3+ --> Interrupt blinatumomab; steroids

ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome)

ICE score used to assess severity

Grade 1 --> Supportive care
Grade 2+ --> Dexamethasone (steroids) + supportive care
Grade 3+ --> Interrupt blinatumomab; steroids

KEY DISTINCTION:

- Tocilizumab treats CRS
- Steroids (dexamethasone) treat ICANS

TUMOR LYSIS SYNDROME (TLS)

Risk factors: high WBC, elevated LDH, hyperleukocytosis
Labs: hyperkalemia, hyperphosphatemia, hyperuricemia, rising creatinine

Step 1 (most important): Aggressive IV hydration (normal saline) — 150–300 mL/hr
Step 2: Allopurinol
Step 3: Rasburicase or sodium polystyrene sulfonate (only after IVF maximized)
Last resort: Renal dialysis (when medical management fails)

ASPARAGINASE TOXICITIES

- Pancreatitis
- Thrombosis

HSCT IN ALL

- Allo-HSCT indications: Ph+, high-risk genetics, relapsed/refractory disease
- T-ALL: allo-HSCT more commonly used in CR1 due to higher relapse risk
- Autologous HSCT: NOT standard in ALL
- MRD negativity is the key goal before transplant

PRACTICE QUESTIONS & ANSWERS

Q1. DH is a 56-year-old male with Ph+ pre-B cell ALL. What is the optimal remission induction therapy?
A. Tretinoin + arsenic trioxide
B. Blinatumomab
C. Clofarabine
D. HyperCVAD + dasatinib

ANSWER: D. HyperCVAD + dasatinib

Rationale:
- Ph+ ALL requires intensive chemo + TKI throughout all phases
- Dasatinib has superior BBB penetration — appropriate given patient's headache symptoms
- Tretinoin + ATO = standard for APL, NOT ALL
- Blinatumomab = for MRD+ (>=3 prior chemo blocks) or relapsed/refractory; not initial induction for a fit patient
- Clofarabine = reserved for relapsed/refractory settings

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Q2. After induction, DH's bone marrow biopsy shows positive MRD. What is most appropriate?
Options: Inotuzumab ozogamicin / Nelarabine / Continue current therapy / Continue C10403 / Continue HyperCVAD + ponatinib / Blinatumomab

ANSWER: Continue current therapy / Continue C10403 / Continue HyperCVAD + ponatinib

Rationale:
- Blinatumomab for MRD+ requires persistent MRD after >=3 blocks of intensive chemo (BLAST trial) DH has only completed induction (1 cycle) — it is premature to switch
- MRD negativity may still be achieved by continuing subsequent HyperCVAD cycles
- Inotuzumab = fulminant relapsed/refractory disease only; not for early post-induction MRD
- Nelarabine = T-ALL only; DH has B-ALL

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Q3. JG is a 33-year-old female with Ph− B-ALL. On day 2 of blinatumomab: fever 39°C, rigors,
emesis, abnormal LFTs (68% blasts prior to therapy). What best describes her symptoms?
A. Differentiation syndrome
B. Cerebellar toxicity
C. Urosepsis
D. Cytokine release syndrome

ANSWER: D. Cytokine release syndrome

Rationale:
- Classic CRS presentation: fever, rigors, emesis, elevated LFTs within first 48 hours of blinatumomab
- Her 68% blast burden is a major risk factor for CRS (widespread immune activation/cytokine storm)
- ICANS presents with lethargy, confusion, speech impairment — not fever and rigors

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Q4. JG has grade 1 CRS. How should it be treated?
A. Supportive care
B. Stop blinatumomab
C. Tocilizumab
D. Dexamethasone

ANSWER: A. Supportive care

Rationale:
- Grade 1 CRS = supportive care only (fluids, empiric antibiotics if febrile)
- Stop blinatumomab: required formally for Grade 3+ CRS only
- Tocilizumab: reserved for Grade 2+ CRS or Grade 1 persisting >3 days
- Dexamethasone: used for ICANS Grade 2+ or higher-grade CRS

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Q5. JG now has Grade 2 ICANS (ICE score 6; lethargic but arousable, does not know year/month).
How should it be treated?
A. Supportive care
B. Permanently stop blinatumomab
C. Tocilizumab
D. Dexamethasone

ANSWER: D. Dexamethasone

Rationale:
- Grade 2 ICANS = dexamethasone (steroids) + supportive care
- Tocilizumab treats CRS, NOT ICANS
- Supportive care alone is insufficient for Grade 2 neurotoxicity
- Permanently stopping blinatumomab is not required for Grade 2 — infusion may be paused and restarted

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Q6. SB is a 28-year-old female with relapsed B-ALL receiving tisagenlecleucel (CAR-T).
Which medication should be initiated on the day of infusion?
A. Corticosteroids
B. Levofloxacin
C. Levetiracetam
D. Rasburicase

ANSWER: C. Levetiracetam

Rationale:
- CAR-T is associated with ICANS — mandatory seizure prophylaxis is required
- Levetiracetam 500–750 mg PO/IV q12h starting on day of infusion, continued >=30 days
- Corticosteroids: AVOIDED prophylactically — impair CAR-T expansion; reserved for emergent toxicities
- Rasburicase: for TLS — not established as required on infusion day in this case

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Q7. DH has Ph+ pre-B ALL on HyperCVAD. Day 2 labs: WBC 42, Cr 2.2, K 5.7, PO4 4.9,
LDH 2810, uric acid 8.6. Along with allopurinol, what is the best TLS management?
A. Aggressive hydration (normal saline)
B. Rasburicase
C. Sodium polystyrene sulfonate
D. Consult for emergent renal dialysis

ANSWER: A. Aggressive hydration (normal saline)

Rationale:
- Aggressive IVF at 150–300 mL/hr is the most critical first intervention
- Dilutes systemic electrolytes; maintains renal blood flow to facilitate excretion of K, PO4, and uric acid
- Rasburicase and sodium polystyrene sulfonate are added ONLY after IVF is maximized
- Dialysis = last resort when medical management fails

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Q8. DH is a 55-year-old male with Ph− B-ALL. Which is the NCCN preferred protocol for his age?
A. CALGB10403
B. CALGB9511 "Larson Protocol"
C. HyperCVAD
D. ECOG1910

ANSWER: D. ECOG1910

Rationale:
- ECOG1910 (blinatumomab consolidation + HyperCVAD) is the only NCCN preferred regimen for adults aged 30–70 with Ph− B-ALL; demonstrated improved OS
- CALGB 10403: for AYA population (15–39 years), not older adults
- HyperCVAD and CALGB 9511: remain recommended options but no longer the single preferred standard

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Q9. DH is a 26-year-old male with Ph+ pre-B ALL. What is the optimal remission induction?
A. CALGB 10403
B. CALGB 9511
C. Mini-CVD + inotuzumab + ponatinib
D. HyperCVAD + ponatinib

ANSWER: D. HyperCVAD + ponatinib

Rationale:
- HyperCVAD + TKI is standard for Ph+ ALL; ponatinib has demonstrated exceptionally high complete molecular response rates
- CALGB 10403 and 9511: specifically excluded Ph+ ALL patients
- Mini-CVD + inotuzumab + ponatinib: designed for older patients; insufficient safety data for the combination

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Q10. Which drug in the ALL induction regimen does NOT affect complete remission rate?
A. Prednisolone
B. Vincristine
C. Daunorubicin
D. Asparaginase

ANSWER: D. Asparaginase

Rationale:
- CR backbone = vincristine + corticosteroid + anthracycline (sufficient to induce high morphologic CR rates)
- Asparaginase improves event-free survival and LFS but does NOT contribute to the initial CR rate

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Q11. KT is a 43-year-old female newly diagnosed with ALL. What are the four key components of treatment?
A. Induction – CNS prophylaxis – Consolidation – Maintenance
B. Induction – Radiation prophylaxis – Consolidation – Maintenance
C. Induction – Radiation prophylaxis – CNS prophylaxis – Consolidation
D. Induction – Radiation prophylaxis – CNS prophylaxis – Maintenance

ANSWER: A. Induction – CNS prophylaxis – Consolidation – Maintenance

Rationale:
- CNS is a sanctuary site requiring mandatory intrathecal chemo — radiation is NOT the standard prophylaxis in adults
- All four phases are essential components of ALL treatment

HIGH-YIELD PEARLS

1. Ph+ ALL requires TKI throughout ALL phases — never omit
2. Dasatinib preferred TKI when CNS symptoms present — crosses the BBB
3. Asparaginase does NOT improve CR rate — improves LFS only
4. Blinatumomab for MRD+ requires >= 3 prior intensive chemo blocks (BLAST trial)
5. Nelarabine = T-ALL ONLY; inotuzumab = R/R B-ALL ONLY
6. Grade 1 CRS → supportive care
Grade 2+ CRS → tocilizumab
Grade >=2 ICANS → dexamethasone
7. Levetiracetam on day of CAR-T infusion — mandatory seizure prophylaxis; NO prophylactic steroids
8. TLS: first step = aggressive IV hydration (normal saline)
9. MRD = strongest overall prognostic factor in ALL
10. ECOG1910 = NCCN preferred for Ph− B-ALL adults aged 30–70
11. High-dose cytarabine can cause cerebellar toxicity
12. In APL, high initial WBC = significant prognostic risk factor for relapse

[heading] EXAM QUESTIONS AND ANSWERS [/heading]

A. DH is a 56-year-old male who presented to the emergency department with complaints of uncustomary fatigue, bone pain, early satiety and headaches. Physical exam revealed splenomegaly, mild hepatomegaly, and lymphadenopathy. Bone marrow biopsy and aspirate revealed ALL with t(9;22). DH has no other pertinent past medical history.

WBC 80.4 x 109/L (4.3 – 10.8 x 109/L)
Differential:  
basophils 0% (0–1%)
eosinophils 0% (1–3%)
lymphocytes 0% (20–40%)
monocytes 0% (4–8%)
neutrophils bands 5% (0%)
segmented 35% (40–60%)
blasts 40% (0–1%)
Platelets 50 K (200–400K)
Hgb 10 gm/dl (13–18 gm/dl)
HCT 28% (37–48%)
BUN 24 mg/dl (8–21 mg/dl)
Scr 1.4 mg/dl (0.5–1.4 mg/dl)
LDH 2079 Units/L (338–610 Units/L)

Which of the following is optimal remission induction therapy to treat DH?

[expand] The correct answer is HyperCVAD + dasatinib.

Rationale

  • Patient Profile: DH is a 26-year-old male (AYA) with Philadelphia chromosome-positive (Ph+) pre-B cell ALL.
  • Standard of Care for Ph+ ALL: For adult and AYA patients with Ph+ disease, clinical guidelines recommend combining an intensive chemotherapy backbone, such as HyperCVAD, with a tyrosine kinase inhibitor (TKI).
  • TKI Selection: TKIs that are well-studied in this frontline setting include imatinib, dasatinib, and ponatinib. Dasatinib is frequently employed because it, along with ponatinib, has superior blood-brain barrier penetration.
  • Differentiating from Other Options:
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B. Bone marrow biopsy after hematopoietic recovery from remission induction therapy revealed positive minimal residual disease. Which of the following is most appropriate to treat DH at this time?

  1. Inotuzumab ozogamicin
  2. Nelarabine
  3. Continue current therapy
  4. Continue C10403
  5. Continue hyperCVAD + ponatinib
  6. Blinatumomab
[expand] The most appropriate treatment for DH at this time is C, D and E

Rationale

  • Premature to Switch: Clinical data does not support initiating blinatumomab or switching therapy if MRD is positive immediately after induction. Many patients with Philadelphia chromosome-positive (Ph+) ALL can still achieve MRD negativity by completing subsequent intensive chemotherapy blocks within their initial protocol (e.g., moving from Arm A to Arm B of HyperCVAD).
  • BLAST Trial Criteria: The standard for adding blinatumomab for MRD-positive disease is based on the BLAST trial, which specifically evaluated patients who had persistent MRD after at least three blocks of intensive chemotherapy. Since DH has only completed one cycle (induction), he should continue his current regimen of HyperCVAD plus a Tyrosine Kinase Inhibitor (TKI).
  • Targeted Agent Timing: Inotuzumab ozogamicin is typically reserved for fulminant relapsed or refractory disease rather than as an early intervention for post-induction MRD.

Why Other Options Are Incorrect

  • Nelarabine: This agent is specifically indicated for T-cell ALL; it would be inappropriate for DH, who has pre-B cell ALL.
  • Blinatumomab: As noted above, starting this now would be considered "overtreating" based on current guidelines, which require persistent MRD after additional chemotherapy cycles.
  • Inotuzumab ozogamicin would only be appropriate in fulminant relapsed or refractory disease.
[/expand]

JG is a 33-year-old female with Philadelphia chromosome-negative pre-B-cell ALL who has undergone multi-agent chemotherapy for remission induction treatment and, unfortunately, relapsed within 3 months of this treatment. JG is planned to receive blinatumomab for her relapsed ALL. She does not have central nervous system involvement and is found to have 68% blasts prior to therapy with blinatumomab. On day 2 of blinatumomab infusion, JG develops emesis with rigors, fever to 39°C, HA, and abnormal liver function tests.

Which of the following best describes JG’s signs and symptoms?

[expand]The correct answer is D. Cytokine release syndrome.

Rationale

  • Classic Timing and Symptoms: JG's presentation of fever (39°C), rigors, emesis, and abnormal liver function tests (LFTs) on day 2 of her infusion is characteristic of grade 1 cytokine release syndrome (CRS). This syndrome typically occurs within the first 48 hours of starting or dose-escalating blinatumomab.
  • Disease Burden: A high disease burden—such as JG's 68% marrow blasts—is a major risk factor for developing CRS, as it results from widespread immune activation and a systemic "cytokine storm".
  • Differentiating from Neurotoxicity: While blinatumomab also causes neurotoxicity (ICANS), ICANS generally presents with lethargy, confusion, or speech impairment rather than isolated fever and rigors, and it often occurs independently of disease burden.

Management Note: For grade 1 CRS, the standard of care is supportive care only, though hospitalization is recommended for the first several days of the first cycle to monitor for escalation.

[/expand]

A. JG is a 33-year-old female with Philadelphia chromosome negative pre B-cell ALL who has received C10403 (refractory), Part B of hyper-CVAD (refractory), and is now admitted for blinatumomab. On day 2 of blinatumomab infusion, JG becomes lethargic but awakens when asked questions. She can name 3 objects, follow commands, write her name, and can count backwards but does not know the year or month. Her ICE score is 6 and is experiencing grade 2 immune effector cell–associated neurotoxicity syndrome (ICANS).

[expand]Which of the following strategies should be employed to treat JG’s CRS?

The correct answer is D. Dexamethasone.

Rationale

  • Grade 2 ICANS Management: JG is exhibiting clear signs of Grade 2 immune effector cell–associated neurotoxicity syndrome (ICANS), including lethargy and a depressed ICE score of 6. The standard of care for Grade 2 ICANS is the initiation of steroids, specifically dexamethasone.
  • Management of Concomitant Symptoms: While the question specifically asks for the strategy to treat her "CRS," the clinical scenario establishes that she has concomitant Grade 2 ICANS. In these cases, steroids are employed because they address the neurotoxicity, whereas tocilizumab (Choice C) is typically reserved for severe/persistent CRS or when CRS and ICANS occur together in specific combinations.
  • Differentiating from Other Options:
    • Supportive care (A): This would only be appropriate for Grade 1 CRS or Grade 1 ICANS; JG’s Grade 2 neurotoxicity requires more active intervention.
    • Stop blinatumomab (B): While the infusion is often paused for CRS, "permanently" stopping is generally not required for a Grade 2 event.
    • Tocilizumab (C): This is the treatment of choice for CRS, but it does not effectively treat ICANS.
[/expand]

JG is a 33 year old female with Philadelphia chromosome negative pre B-cell ALL who has undergone multi-agent chemotherapy for remission induction treatment and unfortunately relapsed within 3 months of this treatment. JG is planned to receive blinatumomab for her relapsed ALL. She does not have central nervous system involvement and is found to have 68% blasts prior to therapy with blinatumomab. On day 2 of blinatumomab infusion, JG develops emesis with rigors, fever to 39 °C, and abnormal liver function tests. She is experiencing grade 1 cytokine release syndrome (CRS).

Which of the following strategies should be employed to treat her CRS?

[expand] The correct answer is A. Supportive care.

Rationale

  • Grade 1 CRS Management: Grade 1 Cytokine Release Syndrome (CRS) should be managed with supportive care only. This typically includes maintenance fluids and empiric antibiotics if fever is present.
  • Why are other options incorrect:
    • Stop blinatumomab (B): Interrupting the infusion is formally required by the prescribing information for Grade 3 or higher CRS.
    • Tocilizumab (C): This is reserved for Grade 2 or higher CRS, or if Grade 1 symptoms persist for more than 3 days.
    • Dexamethasone (D): Steroids are generally used for higher-grade CRS (Grade 3+) or for neurotoxicity (ICANS) Grade 2 or higher.

Since JG's symptoms appeared on day 2, she would likely be hospitalized for monitoring. 

[/expand]

SB is a 28-year-old female with relapsed B-ALL who is undergoing treatment with tisagenlecleucel.

Which of the following medications should be initiated on the day of the CAR-T cell infusion?

  • A. Corticosteroids
  • B. Levofloxacin
  • C. Levetiracetam
  • D. Rasburicase
[expand] The correct answer is C. Levetiracetam.

Rationale

Why Other Options Are Incorrect

  • Corticosteroids (A): Routine use should be avoided as they may interfere with the activity and efficacy of the cellular therapy; they are reserved for managing emergent toxicities.
  • Levofloxacin (B): While some centers use antibacterial prophylaxis, it is not universally indicated by protocol for the day of infusion.
  • Rasburicase (D): This is used for managing tumor lysis syndrome (TLS), but SB’s specific risk for TLS on the day of infusion is not established in the case.
[/expand]

21. This clinical scenario describes tumor lysis syndrome (TLS) in a patient with Philadelphia chromosome-positive pre-B cell ALL receiving intensive chemotherapy (HyperCVAD + TKI). Key Findings Suggestive of TLS:

  • Elevated WBC (42 x 109/L) – high tumor burden
  • High LDH (2810 IU/L) – rapid cell turnover
  • Hyperkalemia (K⁺ 5.7 mEq/L)
  • Hyperphosphatemia (PO₄ 4.9 mg/dL)
  • Hyperuricemia (uric acid 8.6 mg/dL)
  • Rising creatinine (2.2 mg/dL) – signs of acute kidney injury

You are most concerned about her relapse because of:

  1. Her coagulopathy at diagnosis.
  2. The initial WBCs
  3. Her ethnicity
  4. None of the Above.
[expand] The correct answer is 2- The initial WBCs (in APL, a high initial WBC count is a significant prognostic factor for relapse).

Explanation:

  • Coagulopathy (1) is common at diagnosis but does not predict relapse.
  • Initial WBCs (2)—if high (>10,000/μL), indicate a higher risk of relapse in APL.
  • Ethnicity (3) is not a known risk factor for relapse.
  • None of the Above (4) is incorrect because WBC is a validated risk factor Six months later the Pt CBC was normalized and she has tolerated consolidation therapy.
[/expand]

22. DH is diagnosed with Philadelphia chromosome-positive pre-B cell ALL and began HyperCVAD, arm 'A' with a TKI. On day 2 of chemotherapy, his labs were notable for WBC 42 x 109/L, BUN 36 mg/dL, serum creatinine 2.2 mg/dL, potassium 5.7 mEq/L, phosphate 4.9 mg/dL, LDH 2810 IU/L, and uric acid 8.6 mg/dL.
Along with allopurinol, which of the following is best to manage tumor lysis risk in DH?

  • A. Aggressive hydration (normal saline)   
  • B. Rasburicase 
  • C. Sodium polystyrene sulfonate   
  • D. Consult for emergent renal dialysis
[expand] The correct answer is A. Aggressive hydration (normal saline).

Rationale

  • Foundation of Management: For a patient presenting with laboratory signs of tumor lysis syndrome (TLS)—including hyperuricemia (8.6 mg/dL), hyperphosphatemia (4.9 mg/dL), and acute kidney injury (Creatinine 2.2 mg/dL)—aggressive intravenous hydration is the most critical first intervention.
  • Clinical Utility: Intravenous fluids, infused at a rapid rate (typically 150–300 mL/hr), work by diluting systemic electrolytes and maintaining optimal renal blood flow to facilitate the excretion of potassium, phosphate, and uric acid.
  • Priority of Care: While agents like rasburicase (Choice B) are effective for lowering uric acid and sodium polystyrene sulfonate (Choice C) can manage hyperkalemia, they should be utilized only after intravenous fluids have been maximized. Renal dialysis (Choice D) is reserved as a last resort when medical management fails.

DH's high white blood cell count and significantly elevated LDH (> 2810 IU/L) place him in the high-risk category for TLS, making proactive, aggressive hydration essential.

[/expand]

DH is a 55-year-old male with complaints of bone pain, early satiety and frequent headaches. WBC 80.4 x109/L w/ 40% blasts. He is diagnosed with Philadelphia chromosome-negative B-cell ALL.

Which of the following is an NCCN preferred protocol for DH’s age group?

[expand] The correct answer is D. ECOG1910.

Rationale

  • Age-Based Stratification: DH is 55 years old, which places him in the Adult age group (typically 40–65 years) rather than the Adolescent and Young Adult (AYA) group, which is defined as 15–39 years.
  • Preferred Status: For adults with Philadelphia chromosome-negative B-cell ALL, the ECOG1910 protocol (incorporating blinatumomab consolidation) is now the only preferred NCCN regimen.
  • Outcomes: The ECOG1910 trial included patients aged 30–70 and demonstrated that the addition of blinatumomab consolidation significantly improved overall survival compared to standard chemotherapy alone.
  • Differentiating Regimens: While CALGB 10403 (Choice A) is a preferred pediatric-inspired regimen for the AYA population, it is not the standard preferred choice for an older adult like DH. Regimens like Hyper-CVAD (Choice C) and CALGB 9511 (Choice B) remain recommended options but are no longer the single "preferred" standard for this specific patient profile.

Does it make sense why DH’s age and genetic status shifted the recommendation toward ECOG1910, or would you like to review the measurable residual disease (MRD) criteria used in that trial?

[/expand]

DH is a 26 year-old male with complaints of bone pain, early satiety and frequent headaches. WBC 80.4 x109/L w/ 40% blasts. He is diagnosed with Philadelphia chromosome-positive pre-B cell ALL,.

Which of the following is the optimal remission induction therapy?

[expand] The correct answer is D. HyperCVAD + ponatinib.

Rationale

  • Standard of Care for Ph+ ALL: For fit adult and AYA patients with Philadelphia chromosome-positive (Ph+) ALL, the backbone of intensive chemotherapy combined with a tyrosine kinase inhibitor (TKI) is the standard treatment approach.
  • Regimen Choice: HyperCVAD plus a TKI (like imatinib, dasatinib, or ponatinib) is the best-studied intensive regimen for this population. Ponatinib specifically is a highly potent TKI that, when paired with HyperCVAD, has demonstrated exceptionally high rates of complete molecular response and long-term survival.
  • Why Other Options are Incorrect:
    • CALGB 10403 (A) and CALGB 9511 (B): These pediatric-inspired trials specifically excluded patients with Philadelphia chromosome-positive disease.
    • Mini-CVD + inotuzumab + ponatinib (C): This lower-intensity regimen was designed for older patients and the safety of combining inotuzumab with ponatinib is not yet supported by robust clinical data.
[/expand]

34. Which drug in the induction regimen does not affect complete remission response in ALL?

[expand] The correct answer is d. Asparaginase.

Rationale

  • Backbone of Induction: According to clinical guidelines, there are three drugs that constitute the foundational backbone of induction regimens for adult ALL: anthracyclines (such as daunorubicin), vincristine, and corticosteroids (such as prednisolone or dexamethasone).
  • Role of Asparaginase: While asparaginase-based products are often added to these regimens and are critical for improving long-term outcomes like event-free survival (especially in pediatric-inspired protocols), they are not listed as part of the primary backbone required to achieve an initial complete remission (CR).
  • Impact on CR: Historical data indicates that the triplet combination of vincristine, a corticosteroid, and an anthracycline is sufficient to induce high rates of morphologic complete remission; the addition of asparaginase primarily serves to eradicate sub-microscopic disease and prevent relapse.
[/expand]

KT is a 43-year-old female who presents with WBC of 53,000 cells/mm3. Spleenomegaly and lymphadenopathy above and below the diaphragm. Additional work-up reveals a diagnosis of acute lymphocytic leukemia (ALL). Which of the following are the four key components of ALL treatment for KT?

  • A Induction therapy - CNS prophylaxis - Consolidation therapy - Maintenance therapy (88%)
  • B Induction therapy - Radiation prophylaxis - Consolidation therapy - Maintenance therapy (6%)
  • C Induction therapy - Radiation prophylaxis - CNS prophylaxis - Consolidation therapy (3%)
  • D Induction therapy - Radiation prophylaxis - CNS prophylaxis - Maintenance therapy (3%)
[expand] The correct answer is A. Induction therapy - CNS prophylaxis - Consolidation therapy - Maintenance therapy.

Rationale

The treatment of adult ALL is complex and structured into four essential pillars:

  • Remission Induction: The initial phase (4–6 weeks) aimed at eradicating the bulk of leukemic cells and restoring normal hematopoiesis.
  • Consolidation (Intensification): A phase (20–30 weeks) designed to eliminate residual molecular disease and prevent early relapse.
  • Maintenance (Continuation): A long-term phase (2+ years) of lower-intensity therapy to prevent disease recurrence.
  • CNS Prophylaxis: Because the central nervous system is a "sanctuary site" where systemic chemotherapy often fails to penetrate, prophylactic intrathecal chemotherapy is a mandatory component integrated throughout all phases of treatment.
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