The Role of Pre-existing Anti-HLA Antibodies in Severe Aplastic Anemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation [Retrospective study].

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The presence of pre-existing anti-HLA antibodies (Abs) in severe aplastic anemia patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) appears to detrimentally affect platelet recovery and overall prognosis.

The standard first-line treatments for a newly diagnosed patient with severe aplastic anemia (SAA) are HSCT from an HLA-identical sibling donor or immunosuppressive therapy using a combination of horse anti-thymocyte globulin and cyclosporin A. Haploidentical HSCT (haplo-HSCT) is an option for patients where a matched sibling donor or matched unrelated donor is lacking. In this context, the effect of donor-specific anti-HLA Abs is uncertain. A retrospective analysis used data from 244 SAA patients who underwent allo-HSCT between 2016 and 2022. Of these, 82 (34%) tested positive for anti-HLA Abs pretransplant. Patients with anti-HLA Abs with median fluorescence intensity (MFI) over 5000 underwent a desensitization protocol. An MFI of 1000 or above indicated a positive result. The cumulative incidence of platelet engraftment in the positive anti-HLA abs group was 89.8% vs.97.1% in the negative group. The cumulative incidence of transplant-related mortality was 38.3% in the positive Abs group, whereas it was 16.4% in the negative group (p=0.002). Moreover, the overall survival rate (OS) was 57.8% in the positive group and 83.6% in the negative group (p=0.001). The authors found no differences in the cumulative incidence of neutrophil engraftment, acute graft-versus-host disease (GVHD), chronic GVHD, or cytomegalovirus reactivation among both groups. In patients undergoing haplo-HSCT after desensitization, anti-HLA Abs did not affect neutrophil/platelet recovery. Multivariable analysis showed that pre-existing anti-HLA Abs is an independent risk factor for impaired platelet recovery (hazard ratio  [HR] 1.67; 95% confidence interval [CI], 1.16 to 2.44, p=0.006) and OS (HR 2.19; 95% CI, 1.03 to 4.67, p=0.043). Pre-existing anti-HLA Abs did not influence neutrophil engraftment (p=0.600).

Autologous Hematopoietic Cell Transplantation Consolidation for First Response is Associated with Longer Survival Among Patients with Nodal Peripheral T Cell Lymphoma [Retrospective study].  

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Autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation can improve long-term outcomes in patients with nodal peripheral T-cell lymphoma.

Nodal peripheral T cell lymphomas (PTCLs) pose a significant therapeutic challenge due to their aggressive clinical behavior (except anaplastic lymphoma kinase-ALK-positive large cell lymphoma). Auto-HSCT is a potential strategy for consolidating the response achieved with anthracycline-containing chemotherapies (such as CHOP or CHOEP). A retrospective cohort study involving 123 patients with nodal peripheral PTCL treated between 2005 and 2021 (who achieved a complete or partial response to initial chemotherapy) evaluated the impact of upfront auto-HSCT consolidation on overall survival (OS) and event-free survival (EFS). Patients were stratified into two groups based on whether they received auto-HSCT as part of their initial treatment strategy. The authors excluded some subtypes of nodal PTCL, such as enteropathy-associated T cell lymphoma and natural/T cell lymphoma. 30% of patients had high-risk disease (International Prognostic Index [IPI] ≥3) and 87.8% of the cohort achieved complete remission after induction chemotherapy. Auto-HSCT was performed in 85 patients (69%). At a median follow-up of 7.3 years, the median OS for patients who received auto-HSCT after first response was approximately 3-fold longer than those who did not (12.3 vs. 4.3 yr; p=0.035), and the median EFS was also approximately 3-fold longer for patients who received auto-HSCT (6.2 vs. 2.2 yr; p=0.003). In the multivariable analysis, early consolidation after first response with auto-HCT, younger age at diagnosis, female sex, low-risk IPI, and anaplastic lymphoma kinase-ALK-positive anaplastic large cell lymphoma (compared to angioimmunoblastic T cell lymphoma) were associated with superior EFS. The authors suggested that upfront auto-HSCT consolidation during the first response in nodal PTCL is related to better long-term outcomes in transplant-eligible patients.

Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma after salvage autologous hematopoietic stem-cell transplantation [(Myeloma XII [ACCoRD]): interim analysis of a multicenter, open-label, randomized, phase 3 trial].

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Salvage autologous hematopoietic stem cell transplantation (auto-HSCT), combined with an appropriate consolidation and maintenance strategy, possibly continues to have an essential role in the management of relapsed transplantation-eligible myeloma.

Previously, the randomized GMMG phase III trial ReLApsE compared salvage auto-HSCT and lenalidomide maintenance versus lenalidomide/dexamethasone for relapsed multiple myeloma (MM). The trial did not demonstrate prolonged progression-free survival (PFS) and overall survival (OS) on intention-to-treat analysis. Currently, the role of auto-HSCT in the relapsed setting is uncertain. An interim analysis of Myeloma XII (ACCorD)(an open-label, multicenter, randomized, controlled, phase 3 trial) evaluated PFS (the primary endpoint) in an intention-to-treat analysis of patients with relapsed MM that required treatment with salvage auto-HSCT. Initially, patients were randomized (1:1) to receive either conventional auto-HSCT with melphalan or augmented auto-HSCT with melphalan augmented with ixazomib 4 mg given 4 days and 1 day before auto-HSCT (ixazomib is the first oral second-generation proteasome inhibitor). In the second randomization, patients were assigned (1:1) to consolidation using ixazomib, thalidomide, and dexamethasone (ixazomib 4 mg per day on days 1, 8, and 15, plus oral thalidomide and oral dexamethasone), followed by maintenance with single-agent ixazomib (4 mg per day on days 1, 8, and 15)  until disease progression or intolerance or observation. The authors reported data from the initial outcomes of the second randomization in Lancet Haematology and included information from 206 patients (103 in the consolidation and maintenance group and 103 in the observation group). Exclusion criteria for eligibility for 2nd randomization were having received treatment for relapsed disease other than local radiotherapy, therapeutic plasma exchange, or dexamethasone up to a maximum of 160 mg, central nervous system involvement with myeloma, grade 2 peripheral neuropathy within 14 days before 2nd randomization, or failure to have recovered from the reversible effects of previous chemotherapy. Also contraindicates the patient’s participation in this study: prior or concurrent malignancies at other sites (excluding wholly resected non-melanoma skin cancer or carcinoma in situ of any type, such as cervical cancer) and any medical or psychiatric condition which, in the opinion of the investigator would make the participant ineligible. The median follow-up was 27 months (interquartile range, 13–38). Median PFS was 20 months (95% confidence interval [CI], 15–29) in the consolidation and maintenance group and 13 months (95% CI, 11–18) in the observation group (hazard ratio: 0.55; 95% CI, 0.39–0.78; p=0·0006). The most common adverse events in the consolidation and maintenance group were upper respiratory infections without treatment-related deaths. Salvage auto-HSCT combined with a consolidation/maintenance strategy could be a reasonable option vs. other novel therapeutic options at first relapse (e.g., continuous triplet regimens), but more data on long-term follow-up are necessary.

Induction prior autologous hematopoietic cell transplantation in multiple myeloma [Review].

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Quadruplet regimens for induction in multiple myeloma (MM) are associated with deep response and a high rate of sustained measurable residual disease (MRD) negativity. However, cost issues, high-risk disease factors, and the cost-effectiveness and safety of autologous hematopoietic stem cell transplantation are also determinants in the choice of the most appropriate therapy in young and fit MM patients.

Currently, quadruplet regimens combining the anti-CD38 antibody (daratumumab-Dara-) and VRD (bortezomib, lenalidomide, and dexamethasone) or VTD (bortezomib, thalidomide, and dexamethasone) are recommended for induction chemotherapy when available. Before autologous hematopoietic stem cell transplantation (auto-HSCT), induction with triplet regimens to reduce tumor burden was the most popular strategy in this phase of the treatment. However, recent trials with anti-CD38 (CASSIOPEIA, which compared induction with Dara-VTD vs. VTD,  and PERSEUS, which evaluated the induction with Dara-VRD vs. VRD) have shown improvement in the depth of response during induction compared to the standard triplet schemes. The most common adverse events were neutropenia and thrombocytopenia. In the consolidation and maintenance phase after auto-HSCT, treatment with quadruplet therapy for two cycles followed by maintenance with Dara and lenalidomide (PERSEUS trial) could be a strategy for achieving sustained MRD negativity. Another issue is the extension of the induction period (six cycles vs. three or four cycles), given the benefit and low toxicity of the VRD regimen in up to 6 cycles. With this strategy, it is possible to withdraw the consolidation cycles and improve the recovery after auto-HSCT. Modifying the quadruplet schemes could also depend on other factors: costs,  high-risk cytogenetics, circulating malignant plasma cells, and extramedullary disease. For instance, the induction before auto-HSCT with carfilzomib-based quadruplet treatment could achieve sustained MRD negativity in this population. The treatment field in MM is constantly expanding, and the quadruplet regimens have improved outcomes with a manageable adverse effects profile. See Table 1 of the manuscript for access to a comprehensive summary of the pivotal trials of quadruplet therapies for induction, consolidation, and maintenance in MM

Evaluation of prognostic factors in patients with high-risk classical Hodgkin lymphoma undergoing autologous transplantation [Retrospective study].  

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In a contemporary cohort of high-risk patients with classical Hodgkin lymphoma (cHL), advanced age and disease status (less than complete remission)  at autologous hematopoietic stem cell transplantation (auto-HSCT) were predictors of inferior progression-free survival (PFS).

Auto-HSCT is currently considered the standard treatment for relapsed/refractory (R/R) cHL patients. The authors evaluated the risk factors before transplant-associated adverse outcomes in a multicenter retrospective cohort of 478 patients with primary treatment failure (PTF) cHL undergoing auto-HSCT. PTF was defined as 1 of the following three patterns of failure: progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression cohort); partial response or stable disease by imaging after treatment (partial response or stable disease cohort); or progression of disease by imaging within 12 months of completion of chemotherapy after prior documentation of complete response (early relapse cohort). The primary endpoint was PFS, and the secondary endpoints were non-relapse mortality (NRM) and overall survival (OS). Among 478 patients included in the analysis, 217 (45%) had primary progression, 86 (18%) had partial response or stable disease, and 175 (37%) had early relapse. The median follow-up from the time of auto-HSCT among survivors was 34.5 months (range, 0.2-158.5). The median PFS after auto-HSCT was 4.33 years (95% confidence interval [CI], 1.77-10.09). After multivariable analysis, disease status at auto-HSCT was the only prognostic factor for PFS. The 2- and 5-year OS after auto-HCT were 89% (95% CI, 85-92) and 76% (95% CI, 71-81), respectively. After multivariable analysis, age (per 5-year increase, hazard ratio [HR], 1.16; 95% CI, 1.07-1.25; p< 0.001), diagnosis between 2005 to 2010 (compared with diagnosis after 2010, HR, 1.96; 95% CI, 1.21-3.19; p= 0.007), and disease status at auto-HCT (with progressive disease associated with the highest hazard ratio, HR, 5.92; 95% CI, 2.40-15.59; p< 0.001) were related to inferior OS. The study did not find statistically significant factors associated with NRM. The authors concluded that the disease status at auto-HSCT (less than complete remission) was associated with inferior survival (PFS and OS). The incorporation of new therapies (brentuximab vedotin, and checkpoint inhibitors) improves the outcomes in patients with high-risk cHL.

ASTCT and USCLC Clinical Practice Recommendations for Allogeneic Stem Cell Transplant in Mycosis Fungoides and Sézary Syndrome [Guideline]. 

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Allogeneic hematopoietic stem cell transplantation is currently the only available potentially curative treatment modality for Mycosis fungoides and Sézary Syndrome.

Cutaneous T-cell lymphomas (CTCs) are a spectrum of lymphoid malignancies characterized by clonal expansion of T-cells primarily involving the skin. The most typical forms (70%) are mycosis fungoides (MF) and Sézary syndrome (SS). Because there is no published guidance regarding allogeneic hematopoietic stem cell transplant (allo-HCT) for these patients, consensus clinical practice recommendations of the American Society for Transplantation and Cellular Therapy (ASTCT) and the United States Cutaneous Lymphoma Consortium (USCLC) were developed using a Delphi survey of 32 specialists from across the US. The main recommendations were:

Criteria for referral for consideration for allo-HCT:

●      Patients with stage IIB or higher stages

●      Refractory, progression, relapse, or response duration <4 months after at least two lines of systemic therapy

●      Patients with multifocal/generalized stage IIB or higher disease and histological large-cell transformation, N3 or M1 disease (irrespective of the number of prior lines of therapy)

Allo-HCT preparative regimens and procedures:

●      Autologous HCT is not recommended for MF/SS.

●      Reduced intensity/non-myeloablative regimens are preferred for allo-HCT conditioning.

●      Total skin electron beam therapy (TSEBT) to achieve a maximal skin response before allo-HCT conditioning (ranges of 12-36 Gy are generally recommended with courses of 3-6 weeks)

●      Caution with recent use of the anti-CCR4 monoclonal antibody mogamulizumab before allo-HCT because of the higher risk of severe acute graft-versus-host disease (GVHD). The panel recommended spacing between the treatment and allo-HSCT (2-4 months wash-out period).

●      Caution with recent use of checkpoint inhibitors before allo-HCT because of the association of these therapies with higher risk of acute and chronic GVHD (6 weeks wash-out period).

Disease status at the time of allo-HCT: 

●      Preferably, patients should be in complete remission at the time of allo-HCT

●      Patients with limited disease in the skin and/or blood, particularly those with skin involvement who will receive TSEBT, may be considered for allo-HCT.

●      Patients in partial remission from disease in the skin, lymph nodes, and blood may also be considered for allo-HSCT

●      Allo-HCT is not recommended for patients with progressive disease in any compartment.

Multidisciplinary management in the pre-and post-transplant settings:

●      The panel encourages collaboration among dermatologists, hematologists, radiation oncologists, and dermatopathologists in the treatment decisions.

●      Referral to centers with experience in allo-HCT for MF/SS

●      Biopsy for evaluation of skin rashes after allo-HCT and the use of comparative T-cell receptor gene rearrangement studies to help distinguish cutaneous relapse from other etiologies.

Influence of comorbidities on outcome in 1102 patients with an allogeneic hematopoietic stem cell transplantation [Retrospective study].

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There is no difference regarding non-relapse mortality (NRM) between the intermediate- and high-risk (hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) groups. Cardiac comorbidity had the strongest association with NRM.

This is a retrospective analysis of pre-existing comorbidities assessing the relevance of the HCT-CI on the outcome of consecutive patients (n= 1102) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from 2006-2021. Patients had various hematological diseases. HCT-CI was classified as low (HCT-CI=0), intermediate (HCT-CI=1–2) and high-risk (HCT-CI ≥ 3). At 10 years, NRM for low, intermediate, and high-risk HCT-CI groups was 21.0%, 26.0%, and 25.8%, respectively (p = 0.04). NRM difference was significant between low to intermediate (p < 0.001) but not between intermediate to high-risk HCT-CI (p= 0.22). Overall survival (OS) at 10 years differed significantly with 49.9%, 39.8%, and 31.1%, respectively (p < 0.001). In multivariate analysis of HCT-CI organ subgroups, cardiac disease was most strongly associated with NRM (hazard ratio [HR] = 1.73, p= 0.02) and OS (HR = 1.77, p < 0.001). All other comorbidities influenced NRM much less than described in previous studies. Furthermore, donor type (HR = 2.20, p < 0.001 for unrelated and HR = 2.17, p = 0.004 for mismatched related donor), disease status (HR = 1.41, p = 0.03 for advanced disease) and previous HSCT (HR = 1.55, p = 0.009) were associated with NRM.

Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies [Guideline].  

The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines and ASTCT Infectious Diseases Special Interest Group collectively developed an expert opinion panel in the field, to identify key challenges in the management of infections after chimeric antigen receptor (CAR) T-cell therapy. Ten key clinical practice questions were developed, and best practice recommendations were formulated. The responses were formulated based on published literature and mutually agreed upon expert opinions of the panel. Mutual agreement on recommendations was reached through a series of email correspondence. Here are some key points:

See Figure 1 in the original article “Outline of infections occurrence, possible etiologies and management” and Table 3 “Recommended Antimicrobial Prophylaxis Before and After CAR T Therapy.”  

CD19 CAR T-Cells

* Infection density is higher before day (d) 30 versus after d-30; bacterial infections tend to be more frequent during the first 30 d

* After d-30, respiratory viral infections appear most common.

* Fungal infections are <6%  while viral reactivations (herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes virus -6 (HHV-6), cytomegalovirus (CMV), adenovirus) are rare, but occur before and after d-30, (acyclovir prophylaxis is standard practice).

BCMA CAR T-Cells

* Infection rates reported in myeloma clinical trials were high at 58% to 69% (20% to 48% ≥grade 3) but occurred later (median 46-60 days) than those reported after anti-CD19 CAR T-cell therapy; infection density is highest between d-30 and d-100 and declines beyond d-100.

* Respiratory viral infections are prevalent before and after d-30.

* Fungal infections are uncommon (<5%), and virus reactivations (Epstein Barr Virus (EBV), CMV, hepatitis B virus (HBV), and VZV have rarely been observed.

Abbreviations: ANC, absolute neutrophil count; CTI, cell therapy infusion; HBV, hepatitis B virus; HSV, herpes simplex virus; VZV, varicella zoster virus;  BID, twice daily; DS, double strength; PO, per os; QD, once daily; TIW, three times per week; TMP/SMX, trimethoprim/sulfamethoxazole.

⁎ Alternatively, consider close monitoring instead of antibacterial prophylaxis; oral cephalosporins if fluoroquinolones are contraindicated. In children, adolescents and young adults, antibacterial prophylaxis is not universally recommended.

† Consider mold active azoles if prior allo-HCT, prolonged neutropenia, corticosteroid therapy for CAR T-cell-related toxicities, and/or recent history of mold infection. Dosing will depend on echinocandin of choice.

‡ Extended fluconazole prophylaxis is recommended by some experts for those living in coccidioides endemic areas and/or with positive coccidiodes serology in high-risk setting, based on extrapolation from an allo-HCT study which showed high mortality rate

Click here for the abstract

§ If fluconazole is contraindicated.

Fevers occur in 24% to 94% of patients after CAR T-cell infusions, with cytokine release syndrome (CRS) being a common cause that can be refractory or recurrent. CRS usually manifests within the first 2 weeks of CAR T-cell infusion, with a median onset time of 2 to 3 days. CRS treatment with IL-6 and/or steroids may alter or mask the clinical presentation of infection, especially in concomitant neutropenia. Cytokine profiling to differentiate between CRS and severe infection is still evolving and is not utilized routinely to make clinical decisions. Given the predominance of bacterial infections early after CAR T-cell therapy, there should be a low threshold for rapidly initiating broad-spectrum, bactericidal antibiotics per institutional guidelines for managing fever and neutropenia.

Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT [Retrospective study].

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Donor age should be prioritized over major histocompatibility complex, class II, DP beta 1 (HLA-DPB1) matching in patients undergoing 10/10-HLA matched unrelated donor hematopoietic cell transplantation (HCT). HLA-DPB1 matching is associated with relapse and non-relapse mortality within younger, but not older, donor groups.

The authors explored outcomes associated with different combinations of DP-matching and donor age (dichotomized at 35 years) to further guide donor selection. Using a data set from the Center for International Blood and Marrow Transplant Research (see link 2), they categorized 10,783 patients into 6 groups: DP-matched/younger donor (n= 1591), DP-matched/older donor (n= 526), permissive-mismatched/younger donor (n= 3845), permissive-mismatched/older donor (n= 1184), nonpermissive mismatched/younger donor (n= 2659), and nonpermissive mismatched/older donor (n= 978). We noted that younger donor age, rather than DP matching, was associated with better OS. Younger donors with permissive mismatches were associated with improved OS compared with older matched donors. Furthermore, younger donors with nonpermissive mismatches were associated with improved OS compared with older donors with permissive mismatches.

Outcomes of frail patients undergoing high-dose chemotherapy and autologous stem cell transplantation for multiple myeloma [Retrospective study].

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This study demonstrates that in older adults with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (autoHCT), an adapted version of the simplified frailty index (SFI) is predictive of increased non-relapse mortality (NRM) and inferior overall survival (OS) and provides more nuanced information compared with an age-based grouping alone. Even in older adults classified as frail, the expected 100-day NRM from autoHCT is <2%.

In patients with MM not eligible for autoHCT, the SFI identifies frail patients at risk for poor outcomes, but data are limited for transplant-eligible patients. The authors used an adapted SFI that combined age, Eastern Cooperative Oncology Group performance status (converted from the Karnofsky performance status), and an assessment of the hematopoietic cell transplantation-specific comorbidity index. Patients with a score of ≥2 were classified as frail, and those with a score of 0–1 were classified as non-frail.

In this registry-based retrospective study, the authors used an adapted version of the SFI to determine the prevalence of frailty in patients ≥65 years of age with MM, undergoing autoHCT. This study used a dataset made publicly available by the CIBMTR following the publication of the original article by Munshi et al., which described the outcomes of older patients with MM who were undergoing autoHCT.

Out of 5563 patients, 37.9% of patients were classified as frail and although they had increased NRM and inferior OS, the NRM at 100 days remained low (<2%) compared with non-frail patients.

Long-term outcome after allogeneic stem cell transplantation for GATA2 deficiency: An analysis of 67 adults and children from France and Belgium [Retrospective study].

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The factors associated with worse overall survival (OS) in multivariable analysis were the year of HSCT, a history of excess blasts before transplant and peripheral blood stem cell (PBSC) grafts. Bone marrow monitoring to identify clonal evolution and perform HSCT before the appearance of excess blasts is mandatory.

Modalities and timing of HSCT in patients with GATA2 deficiency are still subject to debate. In June 2022, 67 patients (median age 20.6 years) underwent the first allogeneic HSCT among 21 centers. Indications for HSCT were myelodysplastic syndrome (MDS) ≤5% blasts ± immunodeficiency (66%), MDS >5% blasts (15%), and acute myeloid leukemia (19%). The conditioning regimen was myeloablative in 85%, and anti-thymocyte globulins were used in 67%. The cumulative incidence (CI) of acute graft-versus-host disease (GvHD) grade II–IV and III–IV at day 100 were 42% and 13%, and CI of chronic and extensive chronic GvHD at 2 years were 42% and 23%, respectively. The CI of relapse was 3% and 11% at 1 and 5 years, respectively. OS at 1 and 5 years was 83% and 72%, respectively (median follow-up 5.6 years). The factors associated with worse OS in multivariable analysis were the year of HSCT, a history of excess blasts before transplant, and PBSC grafts.

Long‐term outcome of 2‐year survivors after allogeneic hematopoietic cell transplantation for acute leukemia [Retrospective study].

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2‐year survival in remission after hematopoietic cell transplantation (HCT) for acute leukemia is encouraging, with overall survival (OS) of nearly 80% at 10 years. However, the long‐term mortality risk of HCT survivors remains significantly higher than that of the age‐matched general population. Late mortality was predominantly due to relapse and chronic graft‐versus‐host disease (cGVHD).

The authors performed a left‐truncated analysis of long‐term survival in patients with acute leukemia who were alive and disease‐free 2 years after HCT. They included 2701 patients with acute lymphoblastic leukemia (ALL) and 9027 patients with acute myeloid leukemia (AML) who underwent HCT between 2005 and 2012. The 10‐year overall survival (OS) rate was 81.3% for ALL and 76.2% for AML, with the leading causes of late mortality being relapse (ALL‐33.9%, AML‐44.9%) and cGVHD (ALL‐29%, AML‐18%). At 10 years, HCT‐related mortality was 16.8% and 20.4%, respectively. Older age and unrelated donor transplantation were associated with a worse prognosis for both types of leukemia. In addition, transplantation in the second or third complete remission, and peripheral blood stem cells for ALL transplants are associated with worse outcomes. Similarly, adverse cytogenetics, female donor to male patient combination, and reduced intensity conditioning in AML contribute to poor prognosis. Late mortality was predominantly due to relapse and cGVHD. Notably, infections emerged as a significant cause of mortality, particularly in the context of relapsed disease.

Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation [Systematic review and meta-analysis].

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Non-cryopreservation of apheresed autologous peripheral blood stem cell  (PBSC) transplantation appears feasible and safe.

Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of a conditioning regimen prior to cell infusion. Significant cost reduction represents a clear advantage of non-cryopreserved transplants. The aim of this Worldwide Network for Blood & Marrow Transplantation work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. The authors searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Results highlight the collective experience of 19 transplant centers (1686 patients) that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 10⁶/kg. Stem cell viability at transplantation was >90% in multiple myeloma (MM) and >75% in lymphomas after 24–144 hours storage time at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively.  “Fresh” cell autologous transplants require a vigorous logistical coordination effort to achieve all required steps promptly. Also, some conditioning regimens for lymphoma require administration over several days, posing a challenge with prolonged stem cell storage. This limitation is further compounded if the stem cell infusion needs to be postponed for any clinical reason during or after the conditioning regimen has been initiated. Another limitation of non-cryopreserved stem cells is the inability to consider the option of a second or tandem autologous transplant in MM patients; however, the emergence of novel anti-myeloma therapies is obviating the need for a second or tandem transplant in most cases.