---
title: "AlloHCT Feasibility and Outcomes in High-Risk Single- and Double-Refractory CLL"
id: "pubmed-42284699"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42284699"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42284699/"
doi: "10.1182/bloodadvances.2026020219"
published_at: "2026-08-25T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# AlloHCT Feasibility and Outcomes in High-Risk Single- and Double-Refractory CLL
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42284699
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42284699/)
- **DOI:** [10.1182/bloodadvances.2026020219](https://doi.org/10.1182%2Fbloodadvances.2026020219)
- **Published At:** 2026-08-25T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study compared prognosis of chronic lymphocytic leukemia (**CLL**) patients with high-risk genetics (TP53 abnormalities or complex karyotype) who were refractory to one class of targeted agents (single‑refractory high‑risk, **SRHR**) versus those refractory to both classes (**double‑refractory**, **DR**). - The targeted-agent classes considered were covalent Bruton tyrosine kinase inhibitors (**cBTKi**) and B‑cell lymphoma 2 inhibitors (**BCL2i**). - Forty‑seven patients were included: 40 entered as SRHR and 7 entered as DR; 17 of the SRHR patients later progressed to DR, yielding a total DR population of 24. - In the SRHR cohort, 78% were refractory to **cBTKi** and 22% to **BCL2i**; **TP53** abnormalities were present in 90% of SRHR patients. - Median event‑free survival (EFS; progression on next line or death) for SRHR patients was 22 months. - Median overall survival (OS) was 51 months for SRHR patients and 21 months for DR patients, indicating substantially worse survival after development of double‑refractory disease. - Twenty‑two patients underwent allogeneic hematopoietic cell transplantation (**alloHCT**). At 2 years after transplant, nonrelapse mortality was 19%, relapse incidence 19%, progression‑free survival 62%, and OS 67%. - Long‑term progression‑free survivors were observed after **alloHCT**, suggesting transplant can overcome clinical and biological refractoriness in some patients. - Exploratory comparisons between transplanted and nontransplanted patients did not demonstrate a statistically significant OS benefit for **alloHCT** in this dataset. - The authors conclude that prognosis for high‑risk SRHR CLL is poor but better than DR disease; **alloHCT** is feasible in both settings, but its precise benefit and optimal timing remain unresolved based on the reported data. - Detailed methodology, selection criteria for transplant, conditioning regimens, and statistical analyses were not reported in the abstract and therefore are not available from the source provided.
## Clinical Analysis & Structured Key Points
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High-risk single-refractory and double-refractory chronic lymphocytic leukemia: feasibility and impact of alloHCT [Joseph Kauer](https://pubmed.ncbi.nlm.nih.gov/?term=Kauer+J&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Isabelle Krämer](https://pubmed.ncbi.nlm.nih.gov/?term=Kr%C3%A4mer+I&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Patrick Derigs](https://pubmed.ncbi.nlm.nih.gov/?term=Derigs+P&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Maximilian Felix Blank](https://pubmed.ncbi.nlm.nih.gov/?term=Blank+MF&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Sascha Dietrich](https://pubmed.ncbi.nlm.nih.gov/?term=Dietrich+S&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-2 "Department of Hematology, Oncology and Clinical Immunology, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany."), [Julia Meissner](https://pubmed.ncbi.nlm.nih.gov/?term=Meissner+J&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Niklas Kehl](https://pubmed.ncbi.nlm.nih.gov/?term=Kehl+N&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Mirco Julian Friedrich](https://pubmed.ncbi.nlm.nih.gov/?term=Friedrich+MJ&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Maria-Luisa Schubert](https://pubmed.ncbi.nlm.nih.gov/?term=Schubert+ML&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Anthony Dick Ho](https://pubmed.ncbi.nlm.nih.gov/?term=Ho+AD&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Anita Schmitt](https://pubmed.ncbi.nlm.nih.gov/?term=Schmitt+A&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Guido Kobbe](https://pubmed.ncbi.nlm.nih.gov/?term=Kobbe+G&cauthor_id=42284699)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-2 "Department of Hematology, Oncology and Clinical Immunology, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany."), [Carsten Müller-Tidow](https://pubmed.ncbi.nlm.nih.gov/?term=M%C3%BCller-Tidow+C&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Michael Schmitt](https://pubmed.ncbi.nlm.nih.gov/?term=Schmitt+M&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Peter Dreger](https://pubmed.ncbi.nlm.nih.gov/?term=Dreger+P&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#full-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.") Affiliations Expand ### Affiliations * 1 Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany. * 2 Department of Hematology, Oncology and Clinical Immunology, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany. * PMID: **42284699** * DOI: [ 10.1182/bloodadvances.2026020219 ](https://doi.org/10.1182/bloodadvances.2026020219) Free article Item in Clipboard # High-risk single-refractory and double-refractory chronic lymphocytic leukemia: feasibility and impact of alloHCT Joseph Kauer et al. Blood Adv. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42284699/) . 2026 Aug 25;10(16):5698-5705. doi: 10.1182/bloodadvances.2026020219. ### Authors [Joseph Kauer](https://pubmed.ncbi.nlm.nih.gov/?term=Kauer+J&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Isabelle Krämer](https://pubmed.ncbi.nlm.nih.gov/?term=Kr%C3%A4mer+I&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Patrick Derigs](https://pubmed.ncbi.nlm.nih.gov/?term=Derigs+P&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Maximilian Felix Blank](https://pubmed.ncbi.nlm.nih.gov/?term=Blank+MF&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Sascha Dietrich](https://pubmed.ncbi.nlm.nih.gov/?term=Dietrich+S&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-2 "Department of Hematology, Oncology and Clinical Immunology, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany."), [Julia Meissner](https://pubmed.ncbi.nlm.nih.gov/?term=Meissner+J&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Niklas Kehl](https://pubmed.ncbi.nlm.nih.gov/?term=Kehl+N&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Mirco Julian Friedrich](https://pubmed.ncbi.nlm.nih.gov/?term=Friedrich+MJ&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Maria-Luisa Schubert](https://pubmed.ncbi.nlm.nih.gov/?term=Schubert+ML&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Anthony Dick Ho](https://pubmed.ncbi.nlm.nih.gov/?term=Ho+AD&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Anita Schmitt](https://pubmed.ncbi.nlm.nih.gov/?term=Schmitt+A&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Guido Kobbe](https://pubmed.ncbi.nlm.nih.gov/?term=Kobbe+G&cauthor_id=42284699)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-2 "Department of Hematology, Oncology and Clinical Immunology, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany."), [Carsten Müller-Tidow](https://pubmed.ncbi.nlm.nih.gov/?term=M%C3%BCller-Tidow+C&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Michael Schmitt](https://pubmed.ncbi.nlm.nih.gov/?term=Schmitt+M&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany."), [Peter Dreger](https://pubmed.ncbi.nlm.nih.gov/?term=Dreger+P&cauthor_id=42284699)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42284699/#short-view-affiliation-1 "Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.") ### Affiliations * 1 Department of Internal Medicine V, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany. * 2 Department of Hematology, Oncology and Clinical Immunology, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany. * PMID: **42284699** * DOI: [ 10.1182/bloodadvances.2026020219 ](https://doi.org/10.1182/bloodadvances.2026020219) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract This study aimed to compare the prognosis of patients with chronic lymphocytic leukemia (CLL) harboring TP53 abnormalities or a complex karyotype who are refractory to a covalent Bruton kinase inhibitors (cBTKi) or B-cell lymphoma 2 inhibitors (BCL2i; single-refractory high-risk [SRHR] genetics) with that of patients refractory to both cBTKi and BCL2i (double-refractory [DR]), and to investigate the outcome of allogeneic hematopoietic cell transplantation (alloHCT) in these settings. Overall, 47 patients were included. Of these, 40 patients entered the study in SRHR status, and 7 patients in DR status. Because 17 patients evolved from having SRHR to DR status over time, the total DR population comprised 24 patients. In the SRHR cohort, 78% had cBTKi-refractory and 22% had BCL2i-refractory disease, and TP53 abnormalities were in present in 90% of the patients with SRHR. Median event-free survival (defined as progression on next line, or death) of the SRHR cohort was 22 months; and median overall survival (OS) of the SRHR and DR cohorts was 51 and 21 months, respectively. A total of 22 patients underwent alloHCT; their nonrelapse mortality, relapse incidence, progression-free survival, and OS at 2 years was 19%, 19%, 62%, and 67%, respectively. Although long-term progression-free survivors were observed after transplantation, exploratory comparisons of patients who received a transplant and those who did not did not show a significant OS benefit in favor of alloHCT. In conclusion, the outlook of patients with high-risk single-refractory CLL is dismal but better than in patients with DR disease. In both settings, alloHCT is feasible and may overcome clinical and biological disease refractoriness; however, its exact benefit and timing remain to be determined. © 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## MeSH terms * Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42284699/) * Drug Resistance, Neoplasm* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%
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