|
|
IACH News of the Month: Hematopoietic Stem Cell Transplantation (HCT) |
October 9, 2025
Prepared by Dr. Fabio A. Torres and Dr. Uriel Suárez |
|
|
|
|
|
|
|
|
PTCy-based graft-versus-host disease prophylaxis for matched sibling donor allogeneic hematopoietic cell transplantation [Retrospective study] |
Highlights: Schemes for graft-versus-host disease (GVHD) prophylaxis that include post-transplant cyclophosphamide improve outcomes (overall survival [OS] and GVHD-free/relapse-free survival [GRFS]) in matched sibling donor (MSD) transplants. The addition of post-transplant cyclophosphamide (PTCy) is safe and effective for preventing GVHD in haploidentical and matched unrelated donor hematopoietic stem cell transplants (HSCT). The role of PTCy in MSD transplants is unclear. A retrospective cohort with 413 patients that underwent allogeneic HSCT was categorized according to the type of GVHD prophylaxis: group I included calcineurin inhibitor (CNI) and either methotrexate (MTX) or mycophenolate mofetil (MMF); group II included CNI, MTX (or MMF), and antithymocyte globulin (ATG); group III included PTCy, ATG, and CNI; and group IV included PTCy, CNI, and MMF. PTCy (intravenous) was administered at a dose of 50 mg/kg on days +3 and +4. Peripheral blood stem cell grafts from MSDs were used. Primary endpoints were OS, non-relapse mortality (NRM), GRFS, relapse, acute GVHD (aGVHD), and chronic GVHD (cGVHD). The probability of developing grade 3 to 4 aGVHD was significantly lower in patients undergoing PTCy ± ATG (groups III and IV): 17.4% in group I, 3.7% in group II, 3.1% in group III, and 5.1% in group IV (p < 0.001). At 12 months, the cumulative incidence of moderate-severe cGVHD was 38.2% (95%, confidence interval: 33.3-43.1); group I had a rate of 52%, group II had an 18.9% rate, group III had a 13.3% rate, and group IV had a 33.1% rate (p < 0.001). The 1-year GRFS was 15.1% in group I, 50% in group II, 50% in group III, and 49.1% in group IV (p < 0.001). PTCy reduced non-relapse mortality, leading to improved GRFS (hazard Ratio, 0.4; p < .001).The 2-year OS was higher in patients receiving PTCy; 56.6% in group I, 64.6% in group II, 61.4% in group III, and 72.4% in group IV (p = 0.03). Interestingly, the addition of ATG did not influence the efficacy of PTCy in the primary endpoints, except for a lower incidence of both all-grade and moderate-severe cGVHD, but at the expense of more infections (clinically significant cytomegalovirus and Epstein-Barr infections). |
| Click for the full article |
|
|
· Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre, randomised, phase 3 trial [Clinical trial] |
Highlights: Disease-free survival at 1 year was superior in patients with haematological malignancies that underwent transplantation of haploidentical peripheral blood stem cells (PBSCs) plus unrelated cord blood, compared to transplants of PBSCs plus bone marrow. In-vivo T-cell depletion is part of prophylactic strategies for graft-versus-host disease (GVHD) in haploidentical hematopoietic stem cell transplantation (HSCT) and comprises two approaches: the first uses post-transplant cyclophosphamide (PTCy) and the second uses four components for the modulation of T-cell immunity through the GIAC protocol: Granulocyte colony stimulating factor mobilisation of the donor, Intensified post-transplant immunologic suppression, Antithymocyte globulin (ATG) to prevent GVHD and graft rejection, and a Combination of bone marrow and PBSCs as the graft. Previous retrospective studies showed that transplantation of haploidentical PBSCs plus unrelated cord blood was associated with faster platelet engraftment, a lower relapse rate, and better survival, compared with transplantation of haploidentical PBSCs plus bone marrow. A recent open-label, randomised, phase 3 clinical trial in seven centers in China compared these transplant strategies: haploidentical PBSCs plus cord blood (157 patients) vs. haploidentical PBSCs plus bone marrow (157 patients) in patients with acute myeloid leukaemia, acute lymphoblastic leukaemia, mixed phenotype acute leukaemia, and myelodysplastic syndromes. Myeloablative conditioning regimens were used in all participants. For GVHD prophylaxis, ciclosporin A, methotrexate, ATG, and mycophenolate were administered. The primary endpoint was 1-year disease-free survival. The latter was 82.2% (95% confidence interval [CI] 75.2–87.3) in the PBSCs plus unrelated cord blood group and 65.6% (95% CI 57.6–72.5) in the PBSCs plus bone marrow group (hazard ratio [HR] 0.47, 95% CI 0.30–0.74; p= 0.0010). 1- and 2-year overall survival rates were also superior in the PBSCs plus unrelated cord blood group compared to the PBSCs plus bone marrow group (HR 0.50, 95% CI 0.29–0.85; p=0.010, and HR 0.49, 95% CI 0.30–0.79; p=0.003, respectively). The safety profile was also more satisfactory in the PBSCs plus unrelated cord blood group. A mixed graft of haploidentical PBSCs plus unrelated cord blood could achieve better outcomes compared with PBSCs plus bone marrow in patients with hematological malignancies.
|
| Click for the full article |
|
|
Comparison of Chimerism Kinetics and Associated Outcomes in Patients Receiving Post-Transplant Cyclophosphamide Versus Methotrexate based GVHD Prophylaxis Following Allogeneic Hematopoietic Cell Transplant [Retrospective study] |
Highlights: In haploidentical hematopoietic stem cell transplant (HSCT), patients who received a myeloablative conditioning regimen with busulfan/fludarabine (BuFlu) and post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis, mixed CD3 chimerism is associated with an inferior relapse-free survival. Previously, early T lymphocyte chimerism testing at day +90 to +120 has been demonstrated to be a valuable approach for predicting disease recurrence after allogeneic HSCT. The impact of PTCy-based GVHD prophylaxis on the kinetics of donor chimerism is lacking. A retrospective cohort of patients from the Mayo Clinic was studied and transplant associated outcomes were reviewed in relation to the kinetics of donor chimerism in patients who underwent haploidentical HSCT. The outcomes were: time to disease relapse, non-relapse mortality, and death. Full CD3 and CD33 donor chimerism was defined as donor cell fraction ≥ 95%, and mixed chimerism was defined as donor cell fraction < 95% evaluated at day +30, +60, and +90. Five hundred patients were evaluated, of whom 125 (25%) received PTCy, whereas 375 (75%) received methotrexate (MTX) for GVHD prophylaxis. Full donor CD3 T-cell chimerism was more frequently seen in patients with PTCy (day +30: 73.1%; day +90: 74.1%) than in patients with MTX-based GVHD prophylaxis (day +30: 32.5%; day +90: 41.6%) (p<0.001, and p=0.004, respectively). At day +90 post-transplant, patients receiving BuFlu-based reduced-intensity and nonmyeloablative conditioning (RIC/NMA) were associated with an increased risk of mixed chimerism in the MTX group (odds ratio [OR] = 5, p = 0.027), but not in patients receiving PTCy (OR = 0.71, p = 0.7). This excess risk with MTX was not observed in patients receiving myeloablative conditioning (MAC). Interestingly, compared to the patients with full CD3 donor chimerism, mixed donor chimerism in patients with MAC and PTCy was associated with an inferior relapse-free survival (RFS) (1-year RFS: 40.0% vs. 89.16%, p = 0.009). The difference in RFS was not observed in patients with MAC and MTX (1-year RFS: 78.9% vs. 78.2%, p = 0.91) or in patients with RIC/NMA. In conclusion, the kinetics of CD3 donor chimerism in patients with PTCy-based GVHD prophylaxis is a predictive factor in terms of disease relapse, especially with BuFlu-based MAC. |
| Click for the full article |
|
|
TP53-mutant variant allele frequency and cytogenetics determine prognostic groups in MDS/AML for transplantation [Retrospective cohort] |
Highlights: Patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and TP53 mutation have heterogeneous outcomes. It is unclear which patients can achieve a long-term remission through hematopoietic stem cell transplantation (HSCT). In patients who are candidates for HSCT, the absence of both risk factors: high-risk cytogenetics (complex cytogenetics/5q deletion/7q deletion) and TP53 mutation variant allele frequency (VAF) > 50% confers better 2-year progression-free survival (PFS) rates compared to patients who have either of these two risk factors.
Patients with MDS/AML carrying TP53 mutations have a poor prognosis and have high relapse rates with short survival expectancy, even with allogeneic HSCT (allo-HSCT). The prognostic impact of the allelic state of TP53, VAF, number of mutations, and type of mutations is controversial in myeloid neoplasms. A retrospective cohort of 240 patients with TP53-mutated AML (n=126) and MDS (n=114) receiving allo-HSCT was investigated to evaluate the effect of TP53 mutation on PFS. Multihit status of TP53 alterations was defined as follows: presence of >1 TP53 mutation, TP53 mutations with VAF ≥ 50%, or 1 TP53 mutation plus 17p deletion based on cytogenetics. The 2-year PFS for the whole cohort was 24%. Classification and Regression Tee Analysis (CART) was used in multivariate analysis and identified three prognostic groups: TP53 mutation VAF ≥ 50% (2-year PFS of 3%); TP53 mutation with VAF < 50% but having complex cytogenetics or 5q or 7q abnormalities (2-year PFS of 22%), and TP53 mutation VAF < 50% and not having complex/5q/7q cytogenetics (2-year PFS of 60%). TP53-mutated AML/MDS is a group with poor outcomes after transplantation, but it is also a very heterogeneous group, and current data suggest that TP53 mutation should not be the sole criterion for excluding patients from proceeding with allo-HSCT. |
| Click for the full article |
|
|
A survey on the practices and the management of hemorrhagic cystitis in patients who undergo allogeneic hematopoietic stem cell transplantation, on behalf of the Infectious Diseases Working Party of EBMT [Retrospective study] |
Our focus will be on the key points raised in the discussion, contrasting the responses to this survey with the available evidence. The survey response rate was 27% (188/701). The responses were obtained from 103 adult transplant centers, 43 mixed adult and pediatric transplant centers, and 42 pediatric transplant centers.
● 39% of centers declared performing a periodic (mainly weekly), surveillance of BK polyomavirus (BKPyV) load in urine or blood in all patients or at least those considered at higher risk of hemorrhagic cystitis (HC). This policy can be interpreted as the tendency to start the specific antiviral treatment with cidofovir at the first appearance of signs of HC (macrohematuria) in the presence of a known BKPyV infection. ○ The guidelines and the expert consensus do not support screening and surveillance, before and after hematopoietic stem cell transplantation (HCT), of BKPyV in the urine of patients. The reason being that there is no documented efficacy of using a preemptive strategy intervention driven by quantitative PCR.
● Prophylaxis with quinolones is used in 23% of centers and, to a lesser extent, prophylaxis with cidofovir in 3.4%. In comparison, the pre-emptive use of cidofovir is reported in 10% of centers. ○ Hyperhydration and use of sodium 2-mercaptoethanesulphonate (Mesna), especially in patients who received high-dose cyclophosphamide (HD-Cy), are the pillars of prevention measures both in early-onset and in late-onset HC at least as first-line or second-line interventions, while the insertion of a urinary catheter to avoid the contact of urine with the bladder mucosa, inflamed or damaged by cytokines, drug catabolites, and radiation, is less commonly used. The advantages of the preventative use of urinary catheterization are debatable, it may cause patient discomfort and can be not feasible in younger pediatric patients. ○ Quinolones have a mild inhibitory effect in vitro on BKPyV replication, and their use in vivo has been associated with a reduction of BKPyV viruria without any significant impact on the incidence of BKPyV-HC and BKPyV viremia; moreover, the prophylactic use of quinolones is associated with an increase in antibiotic resistance.
● The presence of macrohematuria and the risk of intrabladder clotting justify the adoption of urinary catheterization in 50% of centers, though usually not as a first-line intervention. Overall, use of cidofovir is reported by 85% of centers. In late-onset HC, cidofovir use was based on clinical criteria (overt macrohematuria) or overt HC together with high BKPyV viruria and/or viremia. The fact that 16% and 69% of centers ranked the use of cidofovir in late-onset HC as second-line and third-line or more, respectively, suggests that the antiviral therapy is adopted mainly for the cases of unresponsive or refractory initial supportive care. The most frequent way of using cidofovir is via IV administration at the standard dose of 5 or 3 mg/kg every 1–2 weeks for a maximum of 4–6 doses, but 44% of the centers also report the use of bladder instillation of cidofovir with a daily dose ranging from 1 mg/kg to 5 mg/kg. ○ The therapy of HC remains based on supportive measures such as hyperhydration, Mesna (especially in patients with recent treatment with HD-Cy), analgesics, and maintaining a higher threshold of platelet transfusion. ○ This extensive use of cidofovir somewhat contrasts with the weak recommendation issued for its use in the European Conference on Infections in Leukemia (ECIL; 2018) guidelines due to the absence of robust data on efficacy. This can be justified by the fact that halting virus replication seems consistent with the currently accepted model of the pathogenesis of BKPyV-HC and the unmet need for effective medical intervention in persistent or refractory cases of HC. ○ The efficacy of cidofovir for treating BKPyV-HC is uncertain, and deserves further clinical investigation.
● In this survey, 16% of centers reported at least one cystectomy intervention in the last 5 years. ○ HC has a significant impact on morbidity requiring invasive vascular or surgical intervention, with the risk of residual permanent anatomical lesions of the bladder and kidneys. |
| Click for the full article |
|
|
Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in adults over 70 years old [Editorial] |
|
|
Highlights: In recent years, the improvement in supportive care, nutritional status, donor availability, reduced-intensity conditioning (RIC), post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, and optimal front-line therapy for acute myeloid leukemia (AML) with venetoclax/hypomethylating agent doublet therapies in patients aged ≥ 70 years has increased the use of allogeneic hematopoietic stem cell transplants (allo-HCT) in this population, with lower relapse rates but higher non-relapse mortality (NRM). Currently, few patients aged ≥ 70 years with myeloid neoplasms or myelodysplastic syndromes receive an allo-HCT. In contrast, several improvements, including the advent of RIC, increased donor availability, improved GVHD prophylaxis, enhanced supportive care, and the introduction of new drugs, are challenging the old paradigm of considering age ≥ 70 years as a contraindication for allo-HCT. In AML, the data confirm the feasibility of allo-HCT in this population, with improved leukemia-free survival and lower relapse rates, but higher NRM and no impact on overall survival. For this reason, it is necessary to carefully select the population, considering frailty, patient fitness, comorbidities, drug toxicities, caregiver support, and a standardized pre-HCT assessment to better define the patients who can benefit from transplant. Because post-relapse outcomes are poor, allo-HCT likely benefits patients with a predicted relapse risk of >40% to 45% if the NRM risk is <20%. Regarding the latter, one of the most controversial aspects is refining the current tools for predicting NRM, improving the capacity of scores such as the HCT-specific comorbidity index to include, for example, nutritional data (weight loss, sarcopenia, albumin, and C-reactive protein), thereby improving decision-making regarding allo-HCT candidacy. Essential factors for optimal donor selection include donor age, with lower relapse rates and improved disease-free survival associated with younger donors, cytomegalovirus status, and ABO blood group matching. Post-transplant cyclophosphamide (PTCy)-based prophylaxis shows low GVHD in older adults after haploidentical RIC HCT. The optimal front-line therapy for AML before allo-HCT in older adults has the potential to increase the number of allo-HCT-eligible patients, particularly with venetoclax/hypomethylating agent doublet therapies as the standard of care for lower-intensity induction regimens. Recent prospective trials do not support the existence of an optimal conditioning regimen for older patients. However, a RIC regimen is generally recommended over myeloablative conditioning for better tolerability. Finally, some maintenance strategies could improve outcomes, and in patients with FLT3-mutated AML, post-HCT maintenance therapy with a tyrosine kinase inhibitor should be considered. All patients age ≥ 70 years proceeding to transplant should be enrolled in prospective clinical trials if available. |
| Click for the full article |
|
|
Clinical Practice Recommendations on the Role Of Allogeneic Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Patients With Chronic Lymphocytic Leukemia on Behalf of the American Society for Transplantation and Cellular Therapy [Guideline] |
Highlights: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for chronic lymphocytic leukemia (CLL) patients whose disease has relapsed and/or was refractory to chimeric antigen receptor (CAR) T-cell therapy and in patients with Richter transformation with a complete response (CR) or partial response (PR) to anthracycline-based chemoimmunotherapy or other regimens. Allo-HSCT is a treatment option for relapsing and/or refractory (R/R) CLL or small lymphocytic lymphoma (SLL). However, the emergence of CAR T-cell and targeted therapies (Bruton’s tyrosine kinase [BTK] inhibitors, B-cell leukemia/lymphoma 2 protein [BCL-2] inhibitors, and phosphatidyl-inositol 3-kinase inhibitors) has revolutionized the field of treatment. Since the American Society for Transplantation and Cellular Therapy (ASTCT) clinical practice recommendations for allo-HSCT in patients with CLL were published in 2016, some recommendations have become obsolete. For this reason, the ASTCT Committee on Practice Guidelines has published an update to these Guidelines. Some main recommendations were: ● Disease and treatment settings: Front-line consolidation (regardless of disease risk) 1. Allo-HSCT or CAR T-cell therapy is not recommended for CLL patients achieving CR or PR to a covalent BTK inhibitor/BCL-2 inhibitor alone or in combination. ● Responsive disease after second-line therapy (regardless of disease risk) 2. Allo-HSCT is not recommended for CLL patients who achieve a response after second-line treatment regardless of whether the response followed a BCL-2 inhibitor or a covalent BTK inhibitor. 3. CAR T-cell therapy is not recommended for CLL patients who achieve a response after a second-line treatment regardless of whether the response followed a BCL-2 inhibitor or a covalent BTK inhibitor. ● Responsive disease after third-line therapy (regardless of disease risk) 4. The role of allo-HSCT in CLL patients whose disease relapsed and/or was refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor, but responded to a non-covalent BTK inhibitor, is uncertain. 5. CAR T-cell therapy is recommended for CLL patients whose disease has relapsed and/or was refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor, but responded to a non-covalent BTK inhibitor. ● Nonresponsive disease after second-line therapy (regardless of disease risk) 6. Allo-HSCT is not recommended for CLL patients whose disease has relapsed and/or was refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor. 7. CAR T-cell therapy is recommended for CLL patients whose disease has relapsed and/or was refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor. ● Nonresponsive disease after third-line therapy (regardless of disease risk) 8. Allo-HSCT is not recommended for CLL patients whose disease relapsed and/or was refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor, AND did not respond to a non-covalent BTK inhibitor. 9. CAR T-cell therapy is recommended for CLL patients whose disease has relapsed and/or was refractory to both a covalent BTK inhibitor and a BCL-2 inhibitor, AND did not respond to a non-covalent BTK inhibitor. ● Relapsed or refractory CLL after CAR T-cell therapy 10. Allo-HSCT is recommended for R/R CLL patients after CAR T-cell therapy assuming that the patient is fit for the procedure and demonstrates an objective response prior to the allograft. ● Relapsed or refractory CLL after allo-HSCT failure 11. CAR T-cell therapy is recommended for CLL patients who relapse after an allo-HSCT. ● Front-line consolidation in Richter transformation (RT): role of allo-HSCT or autologous-HSCT in RT patients with objective response to front-line chemoimmunotherapy or other regimens. 12. Allo-HSCT is recommended in CLL patients with RT who achieve a CR or PR to anthracycline-based chemoimmunotherapy or other regimens. 13. The role of autologous HSCT in CLL patients with RT who achieve a CR or PR to anthracycline-based chemoimmunotherapy or other regimens, is uncertain. ● Relapsed or refractory Richter transformation 14. CAR T-cell therapy is recommended for CLL patients with R/R RT.
|
| Click for the full article |
|
|
An ASTCT, CIBMTR, EBMT, and APBMT Consensus Statement Defining Response Criteria for Hematopoietic Cell Transplantation Associated Thrombotic Microangiopathy (TA-TMA) Directed Therapy [Guideline] |
Highlights: For the first time, a consensus of response criteria for transplant associated thrombotic microangiopathy (TA-TMA) directed therapy fills a gap in transplant medicine, which will enable its implementation in clinical trials and registry studies in the future. The definition of clinical response is essential to assess early efficacy of TA-TMA directed therapies. For this reason, consensus on response criteria was achieved by an expert panel from multiple international blood and marrow transplant societies: American Society of Blood and Marrow Transplantation (ASTCT), Center for International Blood and Marrow Transplantation (CIBMTR), European Society for Blood and Marrow Transplantation (EBMT), and Asia Pacific Blood and Marrow Transplantation (APBMT). Some main recommendations were: ● The panel recommends assessing the early efficacy of TA-TMA directed therapy by three terms: complete response (CR), clinically meaningful partial response (PR), and no response (NR) definitions of each TA-TMA hematologic/biochemical and organ manifestation, and an overall response. ● An overall response combines the responses (CR, PR, and NR) in hematologic/biochemical and organ manifestations after TA-TMA-directed therapy. An overall CR requires CR of all TA-TMA manifestations. PR requires the achievement of at least PR in all manifestations. If a patient had an NR of any organ or a biochemical/hematologic NR, the overall response is NR. If patients achieved a mix of CR/PR, the best overall response is PR (see Table 5). ● Hematologic/Biochemical Response Definitions
(see Tables 1 and 2):
1. Complete response: CR of anemia, thrombocytopenia, soluble C5b-9 (< upper limit of normal) AND CR of lactate dehydrogenase (LDH) OR schistocytes. 1.1 Definition of complete response (CR) of anemia: transfusion independence for 14 days and a hemoglobin within normal range for age and sex, which can be achieved at any time point. 1.2 Definition of complete response (CR) of thrombocytopenia: achieving and sustaining a normal platelet count for age without transfusions for ≥14 days. 1.3 Definition of complete response (CR) of schistocytes: undetectable schistocytes at 2 time points within 14 days. 1.4 Definition of complete response (CR) of LDH: normalization of LDH. 1.5 Definition of complete response (CR) of sC5b-9: sC5b-9 level below the upper limit of normal noted at least 2 times within 14 days. 2. Partial response: PR to anemia, thrombocytopenia, soluble C5b-9 (< upper limit of normal) AND PR of lactate dehydrogenase (LDH) OR schistocytes. 2.1 Definition of partial response (PR) of anemia: continued transfusion independence for 7 days and an increase of ≥1 g/dL (≥0.62 mmol/L) of hemoglobin from study entry/TA-TMA diagnosis. 2.2 Definition of partial response (PR) of thrombocytopenia in patients with a platelet count of ≤20,000 cells/uL and/or requiring platelet transfusions within 7 days of treatment: PR is defined as ≥ 7 days transfusion-free and achieving a platelet count of ≥ 20.000 cells/uL. 2.3 Definition of partial response (PR) of thrombocytopenia in patients with a platelet count of ≥ 20,000 cells/uL and ≥ 7 days of platelet transfusion free: PR is defined as ≥ 7 days transfusion-free and either achieving a platelet count of ≥ 50.000 cells/uL OR an increase in platelet count by 50% from start of therapy (whichever is lowest). 2.4 Definition of partial response (PR) of schistocytes: any decrease in schistocyte enumeration using whichever measurement was used at TA-TMA diagnosis. (i.e. any number of schistocytes seen in high-power field, percentage of 1000 red blood cells, or less precise measurements often indicated in automated smear reviews (i.e. +, ++, +++)) 2.5 Definition of partial response (PR) of LDH: persistently elevated LDH with a decrease of at least 25% from TA-TMA diagnosis. 2.6 Definition of partial response (PR) of sC5b-9: persistently elevated sC5b-9 with a reduction of ≥25% of sC5b-9 from diagnosis. 3. No response: Does not meet criteria for hematological/biochemical CR or PR. ● Organ Response Definitions for each organ manifestation (see Tables 3 and 4) Since achieving a nearly overall CR may be challenging/protracted in patients with organ injury; establishment of criteria for clinically meaningful PR is important and may be a more useful early endpoint in studies. Given the complexity of these patients and assessment of response, these definitions may need to be revised in the future after application in large cohorts diverse in age, HCT approaches, and interventional agents. |
| Click for the full article |
|
|
UK recommendations for chimerism testing and monitoring following allogeneic haematopoietic stem cell transplantation (HSCT): Best practice consensus guidelines from the British Society for Blood and Marrow Transplant and Cellular Therapies (BSBMTCT), NHS England Genomic Laboratory Hub (GLH) Haematological Malignancies Working Group, UK Cancer Genetics Group (UKCGG) and the UK National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) |
Key points: ● Peripheral blood (PB) is the specimen of choice for chimerism analysis in most circumstances. ● Chimerism analysis of bone marrow (BM) may be indicated in certain circumstances such as mixed whole blood or myeloid chimerism. ● Analysis of chimerism using fluorescence in situ hybridization techniques is rarely indicated unless molecular genetic testing (e.g. short tandem repeats [STR] analysis) is not suitable. ● STR techniques currently represent standard of care for chimerism analysis in the United Kingdom as they are rapid, reliable, accurate and reproducible despite limited sensitivity of 1%–5%. ● Chimerism analysis using more sensitive molecular techniques such as quantitative polymerase chain reaction (qPCR), digital PCR and next-generation sequencing does not yet offer enough additional benefit to become standard of care. ● Cell separation techniques and lineage-specific enrichment may be carried out using magnetic beads or flow cytometry-based techniques. ● Repeat testing and confirmation of abnormal results is usually necessary prior to clinical intervention. ● Whole blood chimerism (unfractionated PB/BM) performed at day 30 using STR technology is recommended as it can yield useful information regarding engraftment or incipient relapse. ● In malignant disease, assessment of cell subsets or unfractionated whole blood chimerism at day 30 using more sensitive techniques may improve the detection of patients at risk of relapse and should be assessed in clinical trials. ● In malignant disease, mixed myeloid chimerism is always a concern and should trigger further investigation. ● Patients undergoing transplant for malignant disease demonstrating full donor chimerism for 2 years from the time point of last intervention do not need any further chimerism follow-up. ● Recommendations for the use of donor lymphocyte infusions (DLI) in response to mixed chimerism have recently been published by European Society for Blood and Marrow Transplantation and should be referenced in institutional policies. ● In haemoglobinopathies, assessment of whole blood and lineage-specific chimerism in, for example, T-cell fraction (CD3), myeloid fraction (CD15) at day 28, 60, 100 and at least 3 monthly to cessation of immunosuppression is standard of care to guide the management of immunosuppression. ● In malignant diseases in adults assessment of whole blood and lineage-specific chimerism in the T-cell fraction (CD3) and myeloid fraction (CD15) at day 60, 100 and 3 monthly to 2 years is a standard of care. ● In malignant diseases in adults, persistent mixed T-cell chimerism <95% by STR testing or falling donor T cells (>20%) dictates clinical intervention with tapering of immunosuppression ± preDLI. ● Chimerism analysis and measurable residual disease monitoring using molecular methods are important complementary monitoring modalities post-allogeneic stem cell transplant and should be monitored in tandem. |
| Click for the full article |
|
|
Taiwan consensus on pulmonary chronic graft-versus-host disease: A joint statement from the Taiwan Society of Blood and Marrow Transplantation (TBMT) and Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM) [Consensus] |
Key points: See Table 1 and Figure 2 in the original article.
● Diagnosis: ○ Bronchiolitis obliterans syndrome (BOS) is a form of pulmonary chronic graft-versus-host disease (cGVHD) and is commonly accompanied by cGVHD in other organs. ○ The characteristic feature of BOS is a newly developed, irreversible process of respiratory airflow obstruction. ○ The current standard diagnosis of BOS relies on the recommendations of the 2014 National Institutes of Health Chronic GVHD Consensus Guidelines *For patients already diagnosed with cGVHD in other organs, the criteria for diagnosis include all of the following: - Forced expiratory volume in 1sec (FEV1)/Vital capacity (VC) < 0.7 or the lower limit of normal - FEV1 < 75% of predicted with ≥10% decline over <2 years and does not correct to >75% with bronchodilator ○ The use of FEV1/VC < 0.7 as a diagnostic criterion for airflow obstruction is not applicable to all patients. Specific patient populations (either too young or too old) could use FEV1/VC < the lower limit of normal values for the diagnosis of airflow obstruction. ○ If a patient lacks other cGVHD organ involvement, high-resolution computed tomography (inspiratory and expiratory phase) or residual volume measures (>120% of predicted) can aid in diagnosing airflow obstruction. ○ Lung biopsy should not be routinely performed for the diagnosis of BOS. ● Treatment: ○ Combining inhaled corticosteroids and bronchodilators is effective in patients with BOS after hematopoietic stem cell transplantation (HSCT). ○ Adding inhalation therapy (corticosteroids and bronchodilators) to systemic treatment is beneficial for patients with BOS after HSCT. ○ Pulmonary infection should be evaluated when treating patients with BOS. ○ Gastro-oesophageal reflux disease should be evaluated in patients with BOS. ○ Pulmonary rehabilitation is beneficial for patients with BOS. ○ Special considerations (particularly minimized positive end-expiratory ○ pressure) for ventilator support is suggested for patients with respiratory failure. ○ The fluticasone/azithromycin/montelukast (FAM) regimen should be started at the time of BOS diagnosis. ○ Systemic corticosteroids should be combined with FAM regimen once BOS is diagnosed. Other systemic immunosuppressive agents that are used before BOS is diagnosed should be continued. ○ Steroid pulse therapy is an option in addition to the FAM regimen with systemic corticosteroids for moderate or severe BOS. ○ Pulmonary functional tests (PFT) should be performed 4 weeks after treatment is initiated to guide further treatment decisions. ○ If PFT further declined after treatment with FAM and systemic corticosteroids, ruxolitinib can be added. ○ Prolonged use of azithromycin is not suggested if BOS has resolved, due to an increased risk of underlying disease relapse. ○ Lung transplantation should be considered for patients with progressive lung function decline despite pharmacological management or in cases of progression to respiratory failure. |
| Click for the full article |
|
|
|
|
|
IACH Webinars |
Stay tuned for the upcoming IACH webinars |
| Click here |
|
|
|
|
|
