Blood Podcast – “How I Treat” Series on Acute Lymphoblastic Leukemia (ALL)
American Society of Hematology
Date: January 29, 2026
Host: Dr. Hervé Dombret (Blood Associate Editor)

Episode Overview

This special “How I Treat” episode, hosted by Dr. Hervé Dombret, delves into the complexities and latest advancements in the diagnosis and treatment of high-risk subsets of acute lymphoblastic leukemia (ALL), including Philadelphia chromosome–like ALL (Ph-like ALL) and early T-cell precursor ALL (ETP-ALL). Key guests Dr. Sarah Tasian and Dr. David Teachey review recently published guidance, focusing on diagnostic strategies, frontline therapies, allogeneic stem cell transplantation thresholds, and approaches for relapsed/refractory patients.

Key Discussion Points & Insights

1. Introduction to “How I Treat” Series on ALL (00:23–02:47)

• Dr. Dombret introduces the six-part series published in Blood, focusing on particularly high-risk and clinically challenging ALL subgroups.
• Notable subtypes covered: Ph+ ALL, Ph-like ALL, infant ALL, ETP-ALL, ALL in older patients, and post-immunotherapy relapsed B-cell precursor ALL.
• Aim: Provide practical guidance for diagnosis and management across these complex subgroups.

2. Ph-like ALL: Diagnostic Complexities and Evolving Approaches (02:47–06:56)

Dr. Sarah Tasian summarizes her “How I Treat” article:

• Emphasizes the diagnostic challenges and case-based approaches for Ph-like ALL, a subgroup identified by kinase-activated gene expressions similar to Ph+ ALL, but lacking the classic BCR-ABL1 fusion.
• Article highlights clinical management both inside and outside of trials, focusing on:
  • The role of tyrosine kinase inhibitor (TKI)-based strategies.
  • The integration of immunotherapies (e.g., blinatumomab) into frontline and relapse settings.
  • “Complexities in BCR-ABL–like or Ph-like ALL have become much more manageable with advances in genomics and therapies.” (03:22, Dr. Tasian)

Major diagnostic takeaways (06:56–09:27)

• Diagnosis now relies on genomics, not just immunophenotype or legacy gene expression arrays:
  • Two main genetic “bins”: CRLF2/JAK-STAT pathway alterations and ABL-class fusions.
  • CRLF2 rearrangements can be rapidly identified via diagnostic immunophenotyping (increased TSLPR expression).
  • “At this point, we have largely abandoned the older expression arrays that were very helpful for screening. Now that we can move directly to next generation technologies.” (09:20, Dr. Tasian)
• Rapid next-generation sequencing (NGS) now standard, affording quicker diagnosis and personalized targeting.

3. ETP-ALL: Classification & Management Insights (04:05–06:40)

Dr. David Teachey highlights his How I Treat and Genomics review articles:

• Clinic-classified by immunophenotype: Early T-cell precursor ALL (ETP-ALL) vs. more mature T-ALL.
• ETP-ALL:
  • Similar frontline outcomes to other T-ALL subtypes but distinct event profiles—more likely refractory disease vs. relapses.
  • Genomic reclassification splits ETP-ALL into “three broad genetic groups—TXL3 group A, BC11B group, and ETP-like—each with unique clinical implications.” (05:17, Dr. Teachey)
  • ETP-like group has highest therapy resistance/dysregulation (e.g., JAK-STAT) and may respond to BCL2 inhibitors like venetoclax.

Major Therapeutic Advances & Current Trials

4. Frontline Treatment Approaches: Combining the New Arsenal (09:27–13:49)

Ph-like ALL

• Shift from standard chemotherapies toward precision medicine:
  • Early TKI incorporation akin to Ph+ ALL, based on rapid genomic testing.
  • Blinatumomab (BLINA) “has revolutionized treatment across the age spectrum,” especially in adults—trials ongoing for fusion-specific TKI use with chemo and blinatumomab in pediatric/AYA settings.
  • Ongoing investigations into JAK inhibition (e.g., ruxolitinib) for CRLF2/JAK-subgroup—less clarity outside ABL-class fusions.
  • “No uniform standard of care yet established, but combining all available weapons—chemotherapy, TKIs, immunotherapy—is becoming the model.” (10:42, Dr. Tasian)

ETP-ALL

• Despite increased induction resistance (slow response/MRD clearance), long-term outcomes similar to other T-ALL if MRD-negative by consolidation.

5. Role of Allogeneic Stem Cell Transplantation: Re-defining Indications (13:49–19:32)

MRD-driven decision-making

• Historically, patients with persistent MRD (especially end-of-consolidation) were considered for immediate transplant.
• Dr. Teachey (ETP-ALL):
  • “If you still have persistent disease after a period of time, that's a bad sign… if the disease comes back, you need a transplant.” (16:11; 22:32)
  • Children’s Oncology Group data: patients who remained MRD-positive despite intensified chemo and received transplant had ~90% overall survival; those kept on chemo alone had <20%.
• Dr. Tasian (Ph-like ALL):
  • “CD19 CAR T-cell immunotherapies and other strategies are shrinking our transplant indications, but for persistent MRD or tough genotypes, transplant remains key.” (17:06, Dr. Tasian)
  • Early TKI/targeted therapy introduction and immunotherapy are reducing the percent of patients needing transplant to ~5%.

6. Emerging Strategies for Relapsed/Refractory Disease (19:32–25:40)

Ph-like ALL (Dr. Tasian)

• Historically dismal outcomes (30–50% 5-year survival), now improving with immunotherapies:
  • Blinatumomab, inotuzumab, CD19 and CD22 CAR T cells, showing similar remission rates regardless of adverse genetics like Ph-like status.
  • Debate ongoing regarding optimal sequencing/generation of TKIs for relapse (e.g., dasatinib, ponatinib, asciminib).

ETP-ALL (Dr. Teachey)

• “For relapse, transplant is the only curative therapy. The challenge is simply getting these patients into remission.” (22:32, Dr. Teachey)
• Relapsed ETP-ALL:
  • Try traditional chemo, but rapid adoption of targeted therapy (venetoclax/BCL2 inhibitors) and JAK inhibitors for appropriate subsets.
  • Immunotherapy in T-ALL is lagging behind B-ALL due to technical challenges (CAR T-cell “fratricide,” T-cell aplasia), but off-the-shelf and donor-derived products (CD7 CARs, anti-CD38 antibodies e.g., daratumumab) are rapidly emerging.
  • “Even more exciting... immunotherapies in T-ALL. CD7 CARs are very exciting, and there's data with daratumumab from the DELPHINIST trial.” (25:06, Dr. Teachey)

Notable Quotes & Memorable Moments

• “At this point, I think we have largely abandoned the older expression arrays... Now we can move directly to next generation technologies.”
  — Dr. Sarah Tasian (09:20)

• “In T-ALL, if the disease comes back, you need a transplant... 90% overall survival for patients who went to transplant versus less than 20% for chemotherapy alone.”
  — Dr. David Teachey (16:11)

• “Blinatumomab addition to chemotherapy and now in combination with TKIs... is rapidly becoming a new precedent for us, and one we would like to validate formally.”
  — Dr. Sarah Tasian (12:19)

• “Immunotherapies in T-ALL have been behind B-ALL for a number of reasons... but CD7 CARs and daratumumab are promising.”
  — Dr. David Teachey (25:06)

Timestamps for Key Segments

• 00:23 – Introduction to “How I Treat” series and overview of ALL subtypes
• 02:47 – Dr. Tasian’s summary of Ph-like ALL approaches and challenges
• 04:05 – Dr. Teachey outlines ETP-ALL classification and new genomic findings
• 06:56 – Evolving diagnostics: Immunophenotype vs. genomics in subclassifying Ph-like ALL
• 09:27 – Therapeutic arsenal: Chemotherapy, TKIs, and immunotherapies
• 13:49 – MRD and transplant decisions in high-risk ALL subtypes
• 17:04 – Data-driven thresholds for stem cell transplant in ETP-ALL (Teachey) and Ph-like ALL (Tasian)
• 19:32 – Relapsed/refractory strategies: CAR T, TKIs, and new immunotherapies
• 22:29 – Targeted and novel immunotherapies in ETP-ALL relapse
• 25:40 – Final thoughts and call to read the How I Treat series

Summary Flow & Tone

• The discussion is dynamic, collegial, and highly educational, emphasizing data-driven, nuanced treatment decision-making.
• Major themes: rapid advances in genomic classification are translating into more personalized, precise approaches to therapy; immunotherapy is increasingly central in both upfront and relapse settings, with shifting indications for transplant.
• The episode is peppered with clinical pearls (“persistent MRD after consolidation is a key threshold,” “rapid diagnosis via NGS allows for early tailored therapy”) and a shared optimism about the ongoing revolution in ALL care.

To learn more, explore the full How I Treat series in Blood at www.bloodjournal.org.