PETAL Consortium Survival Prognosticators and How Inflammation Impacts Hematopoiesis

Summary

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Blood Podcast Episode Summary

PETAL Consortium Survival Prognosticators and How Inflammation Impacts Hematopoiesis

Date: March 5, 2026
Host: Dr. Laura Michaels
Guests: Dr. Emmanuel Pasigue (Columbia University) and Dr. Marc Sorial (Dana Farber Cancer Institute)
Podcast by: American Society of Hematology

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Episode Overview

This episode of the Blood Podcast highlights two recently published studies in the field of hematology. The first half focuses on how inflammation impacts hematopoiesis by remodeling specific compartments of the bone marrow niche, as discussed by Dr. Emmanuel Pasigue. The second half addresses prognosticators of survival in nodal mature T cell lymphomas, with a deep dive into early relapse as a predictor for poor prognosis, presented by Dr. Marc Sorial and based on findings from the PETAL Consortium.

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Part 1: Inflammation and the Bone Marrow Niche

Guest: Dr. Emmanuel Pasigue
Article: “Inflammation perturbs Hematopoiesis by remodeling specific compartments of the Bone marrow niche”
Segment start: [00:34]

Key Discussion Points & Insights

Motivation and Historical Context

• Dr. Pasigue’s work is described as "a story of love" spanning nearly 10 years across UCSF and Columbia University ([01:20]).
• The team's original motivation was to resolve inconsistencies in identifying bone marrow niche populations across studies, aiming to build a comprehensive, usable "atlas" for the field.

Creation of the Bone Marrow Niche Atlas

• The atlas integrates data on niche populations in mouse models, providing:
  • Standardized isolation protocols.
  • Clarified naming conventions.
  • An open resource for researchers to identify and study specific cell populations ([01:20]-[02:30]).

Unexpected Scientific Findings

• While building the atlas, the team focused on the leptin receptor-expressing mesenchymal stromal cell (MSC) population. This is the most abundant MSC in the adult bone marrow.
• Discovery: Under acute inflammatory conditions (notably, interferon signaling), these MSCs:
  • Become “inflamed,” expressing Sca-1 as a marker.
  • Lose their differentiation capacity toward osteoblasts and adipocytes.
  • Upregulate chemokines essential for monocyte retention.
• Functional impact: Inflamed MSCs retain tissue-damaging monocytes within the marrow, contributing to marrow dysfunction during acute inflammation ([02:30]-[04:09]).

Broader Implications & Next Steps

• The atlas, originally devised as a methods resource, also brings significant new biology to the field ([04:25]).
• Future directions include dissecting heterogeneity between bone marrow compartments (e.g., pelvis vs. femur) and optimizing protocols for distinct anatomical sites ([05:20]-[06:21]).

Notable Quotes & Moments

• Dr. Pasigue:

  “This work is, I will say, a story of love. We have been working on it for almost 10 years in two different institutions...we realized that the field didn’t have a really good reference dataset…we decided to tackle that in a very rigorous manner to provide [an] atlas very usable by everybody in the field.” ([01:20])

• Dr. Pasigue:

  “This population could really become inflamed...express Sca-1 as a marker of inflammation...they stop differentiating, they change their fates...they start expressing a lot of chemokine, which are very important for monocyte retention.” ([02:45])

• Dr. Pasigue (about future studies):

  “Now that we have that, the next step is building the understanding for single bones.” ([06:03])

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Part 2: PETAL Consortium—Prognosticators in Nodal Mature T Cell Lymphomas

Guest: Dr. Marc Sorial
Article: “Early Time to Relapse as a Survival Prognosticator in Nodal Mature T Cell Lymphomas: Results from the PETAL Consortium”
Segment start: [06:30]

Key Discussion Points & Insights

Background & Data Sources

• The PETAL Consortium is a global partnership involving academic centers across six continents ([07:02]).
• The study draws on:
  • Retrospective data: ~1,000 patients from PETAL, 500 from the GEL group, plus data from LISA’s phase III trial as validation.
  • Collaboration was vital due to nodal mature T cell lymphoma’s rarity.

Challenge of Disease Heterogeneity

• T cell lymphomas present with extreme heterogeneity—many subtypes, unique markers, and different natural histories—complicating trial enrollment and scientific advances ([08:08]).

Key Finding: Early Relapse as a Prognostic Marker

• Relapse within 12 months ("early relapse") was a robust predictor of poor overall survival, regardless of:
  • Lymphoma histology,
  • Whether the patient had transplant consolidation,
  • PIT (Prognostic Index for T-cell lymphoma) score ([08:35]-[09:11]).
• Dr. Sorial:

  "We found that this was an important marker that...delineated good vs. bad survival, irrespective of histology, irrespective if they had transplant consolidation...really in every situation that we looked, we found that early relapse confirmed worse survival." ([08:51])

Impact of Second-Line Treatment

• Data showed that patients with early relapse had worse survival with second-line chemotherapy than with non-chemo approaches (e.g., HDAC inhibitors, PI3 kinase inhibitors).
• Among late relapsers, second-line treatment outcomes were similar regardless of chemo or non-chemo regimen ([09:29]-[10:44]).
• Dr. Sorial:

  "People who relapse early—survival from second line with chemo was much worse than non chemo. Whereas in people who relapse late, the survival was actually similar irrespective of what you got." ([09:39])

Addressing Surveillance and Real-World Practice

• Time to progression in the retrospective data was defined as:
  • Either first documented progression (imaging or clinical) OR
  • Start of next-line therapy
• Recognizes the practical challenges of variable scan intervals and incomplete data, emphasizing a flexible and inclusive approach ([11:11]-[12:17]).
• In the ongoing prospective arm, scan dates are recorded to permit normalization in future analyses.

Implications for Clinical Trials

• Allows earlier and more accurate identification of poor-prognosis patients.
• Supports more targeted and realistic endpoints for trials, and may guide which patients to prioritize for intensive or novel therapies ([12:17]).

Notable Quotes & Moments

• Dr. Sorial:

  "The PETAL Consortium...was a global effort from over 100 of those investigators together... The data here we used, the retrospective portion was about 1,000 patients from Petal..." ([07:02])

• Dr. Sorial:

  "Absolutely. Some of the big challenges with T cell lymphoma: 1 is the relative rarity makes it hard to accrue onto trials, but also the heterogeneity within the disease." ([08:08])

• Dr. Sorial:

  "I think the value of a practical tool is that it can be flexible whether or not you start therapy or you have clinical progression or an imaging." ([12:17])

• Dr. Michaels:

  "Early markers for later progression allow trial design to have more realistic endpoints and to also target those who are likely to relapse or have poorer survival for more aggressive treatments." ([12:17])

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Timestamps for Important Segments

• [00:34] — Dr. Emmanuel Pasigue discusses the bone marrow niche atlas and inflammation’s effects.
• [02:30] — Discovery of inflamed leptin receptor+ MSCs and impact on hematopoiesis.
• [05:20] — Discussion on marrow compartment heterogeneity and future research.
• [06:30] — Dr. Marc Sorial introduces the PETAL Consortium and nodal mature T cell lymphoma study.
• [08:35] — Early relapse as a universal prognostic marker.
• [09:29] — Second-line therapy outcomes in early vs. late relapsers.
• [11:11] — Methodology for defining progression and challenges of real-world data.

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Conclusion

This episode delivers an in-depth look at two major areas in hematology: the effect of inflammation on bone marrow microenvironments and international consensus on survival prognosticators in nodal mature T cell lymphomas. Both segments highlight the importance of large-scale collaboration, rigorous methods, and real-world relevance in advancing hematology research.

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Transcript

[A]

Welcome to the American Society of Hematology Conversations with Blood Authors podcast hosted by Dr. Laura Michaels. In this episode, she discusses the article Inflammation perturbs Hematopoiesis by remodeling specific compartments of the Bone marrow niche with Dr. Emmanuel Pasigue. She also discusses the article Early Time to Relapse as a Survival Prognosticator in Nodal Mature T Cell Lymphomas results from the PEDAL consortium with Dr. Marc Sorial.

[B]

I'm so happy to welcome Dr. Emmanuel Pasigue to the Blood podcast. Dr. Pasigue and her collaborators are at the Columbia Stem Cell Initiative in the Department of Genetics and Development at Columbia University and she's going to be speaking about the work that they've demonstrated showing how how inflammation perturbs hematopoiesis in specific compartments of the bone marrow niche. Thank you very much for joining us, Dr. Pasigi. It appears that one of the central questions that your team was looking to answer was about how hematopoietic stem cells interact with the different compartments of the bone marrow stroma. Do I have that right?

[C]

In large part. Hello, Laura. It's a pleasure to be on the podcast. Thank you. This work is, I will say, a story of love. We have been working on it for almost 10 years in two different institutions. I started at UCSF and then the work came with me when I moved to Columbia University. We were always interested by the interaction between hematopoietic stem cell and the downstream progenitor and the bone marrow niche microenvironment. A previous paper on the leukemic niche, a recent article on the aging bone mar niche and over this work we realized that the field didn't have really good reference data set which were integrated which provide a resource for people to really know which niche population to study how to isolate it. There were many different isolation protocol naming convention was all over the map. So it was kind of like difficult. We decided to like tackle that in a very rigorous manner to provide like atlas very usable by everybody in the field working on mouse model to study the different niche population. And then we got a scientific finding. Then we got interested by an observation that one of these niche population, this leptin receptor explains expressing mesenchymal stroma cell which is the most abundant mesenchymal stroma cell in the anti open marrow cavity. We wrapped around endothelial cell forming the sinusoidal blood vessel. This population could really become inflamed Express scar 1 as a marker of inflammation. And so we went after what was happening to this cell and the consequence for the hematopoietic system. And we found that it's a response, acute response to an inflammatory challenge, essentially an interferon signaling. And the cell become like very changed in their fate. They stop differentiating towards various type of downstream progeny, like osteoblast adipocytes, which normally form the melia, the environment of the marrow. They stop differentiate, they change their fates. They start expressing a lot of chemokine, which are very important for monocyte retention. And what we found is that during an acute inflammation, this cell really help to keep in the marrow cavity a population of tissue damaged, damaging monocyte, which contribute to the alteration associated with an acute inflammation.

[B]

So you use this originally your idea is to come up with this atlas and then you use that atlas to investigate this one particular thing. But it seems like the atlas would open up investigations for a whole lot of additional questions, correct?

[C]

Absolutely. This was initially we submitted as a resource method paper because we really wanted the visibility on the atlas, which I think it's fantastic for the community. And, and we got already a lot of feedback on the usefulness of the atlas. But when you publish a method piece, you always want to bring some new biology. And that was really this new biology about this inflame niche population.

[B]

It's just so fascinating. I did have one question before we end, and I know people will have a ton more as they read your work, but in the model, as I understood it, the cells that you investigated were homogenized from different marrow compartments in the mouse. Is it possible that the marrow compartments are different depending on the location in the body, that is in the pelvis versus the femur.

[C]

Absolutely. And that now is the next step of this kind of investigation. When we have the groundwork, especially what we did, separating endothelial compartment versus central marrow compartment, which is this like different isolation process for the very stuff and gooey central marrow that you need to digest very lightly in order to not kill all the surface marker or even the population versus much harsher isolation technique for cell which are stuck along the bone. Very different extracellular matrix composition, you need to dissociate them more harshly. Now that this methodology is in place, and the goal for this paper was cell number, we wanted to get as many cells as possible to be able to get this molecular signature, this understanding of this niche composition. Now that we have that, the next step is building the understanding for single bones.

[B]

Wonderful. Thank you so much for your time and for bringing this new data to the community.

[C]

Thank you.

[B]

I'm so happy to welcome Dr. Mark Sorial of the Dana Farber Cancer Institute. He's going to discuss the work of his group on early time to relapse as a survival prognosticator in mature T cell and NK cell lymphomas. Dr. Soriel, thank you and welcome. I understand that these are results from a consortium that is called the PETAL Consortium. Can you tell me a little bit about where for your analysis comes from?

[D]

Thank you for inviting me on the podcast. The PETAL Consortium is a global consortium that encompasses sites, academic medical centers from six continents, many countries. And this was a global effort from over 100 of those investigators together. The PETAL consortium. Initially, the first data set we created was a retrospective observational data set from all these academic sites that was collaboratively collected. We have an ongoing prospective trial also collecting from these sites, as well as new sites that have joined since then. But the data here we used, the retrospective portion was about 1,000 patients from Petal. And then we also collaborated with our colleagues in Latin America, the gel group, G E L L, who offered another 500, I believe, cases. And then we had also collaboration from the LISA group who used their phase three randomized road chop versus CHOP as a validation arm. So that was the data.

[B]

So it seems like a consortium like that would be necessary when you're dealing with a relatively rare subtype of disease like nodal mature T cell lymphomas.

[D]

Absolutely. Some of the big challenges with T cell lymphoma 1 is the relative rarity makes it hard to accrue onto trials, but also the heterogeneity within the disease. So how many subtypes that we know of? I mean, there's still ptcl, not otherwise specified. That's one of the major histologies that we haven't described yet fully. So that heterogeneity, and they're all kind of have their unique markers and unique disease kinetics, it makes it hard to advance science.

[B]

From what I could gather, the general finding here was that early relapse, so relapse within 12 months was a very important and reliable marker of poor overall survival. Have I got that right?

[D]

Correct. I would highlight the reliability of the marker. We found that this was an important marker that delay needed good versus bad survival, irrespective of histology, irrespective if they had transplant consolidation after front line, irrespective of PIT score. Really, in every situation that we looked, we found that early relapse confirmed worse survival.

[B]

What is the PIT Score prognostic index

[D]

for T cell lymphoma. It's an alternative score to like the IPI score, for example.

[B]

Was there any characteristic of second line treatment that could rescue that destiny for people that had earlier relapse?

[D]

We think so. Our data, one of the analyses that we put I think in the supplement looked at the survival based on second line therapy in people who had early or late relapse. And this is kind of inspired by what we do in other disease states. So like the fusage B cell, if you have early relapse at the front line, you just go like you would go to car, for example follicular you maybe you not you don't use chemo again in the second line. That was kind of the inspiration for why we looked at early versus late relapse after at second line. Because of the heterogeneity and also because of the unfortunate difference in availability for therapies across the world, we couldn't really look more than lumping people together as chemo and non chemo. The most common non chemo is generally would be like HDAC inhibitor ormudepsin, something like that, or like a PI3 kinase inhibitor like duvelisib. Those have been coming up more recent studies, but we kind of lumped them all together, which is not great. But at least we can look at chemo versus non chemo. We found that people who relapse early survival from second line with chemo was much worse than non chemo. Whereas in people who relapse late, the survival was actually similar irrespective of what you got. So there's implications there for deciding therapy, but also trial design and streamlining who you include, how you design the trials.

[B]

Yeah, exactly. One of the things about retrospective studies that use disease progression as an outcome is that not every participant is scanned at the same cadence or that there's like regular monitoring. Does your consortium specify when disease monitoring is going to be done? Is it uniform or is that something that can only be done in a prospective setting?

[D]

It's a great question. We have an approach to this which I think I'm fairly proud of. In the retrospective data, what we defined as time to progression was either time to first documented progression imaging or clinical progression or time to start of next line therapy. So if they didn't have imaging, if there wasn't documented progression, we used the start of the second line therapy as their marker for progression. In the retrospective data, this was a majority of patients where their time to relapse within 12 months was based on starting next line therapy. So it's possible they relapsed or they had progression even sooner than that. Regardless, we used both as a definition. So both in clinical practice would be fair if you had someone who needed urgent therapy, didn't get a scan that you could still use that to apply to their early relapse. In the prospective portion, we are collecting every scan that's done, that's shared with us, and we have a date associated with each scan. So there's potential that we can normalize the time to progression or when the scans are being done to a degree. But I think the value of a practical tool is that it can be flexible whether or not you start therapy or you have clinical progression or an imaging.

[B]

Absolutely. Especially as your article points out, early markers for later progression allow trial design to have more realistic endpoints and to also target those who are likely to relapse or have poorer survival for more aggressive treatments. Thank you so much, Dr. Soriel. I really appreciate the opportunity to explore this work with you.

[D]

Thank you.

[A]

Thank you for listening to this episode of Conversations with Blood Authors. To read the articles, visit bloodjournal.org this episode is copyrighted by the American Society of Hematology.