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Current Opinion in Hematology Nov 2013Allogeneic hematopoietic cell transplantation (HCT) can potentially cure indolent non-Hodgkin lymphoma (NHL). However, the optimal timing and indications remain unclear.... (Review)
Review
PURPOSE OF REVIEW
Allogeneic hematopoietic cell transplantation (HCT) can potentially cure indolent non-Hodgkin lymphoma (NHL). However, the optimal timing and indications remain unclear. Here, we review recent published reports on the subject and summarize our approach.
RECENT FINDINGS
Recent prospective clinical trials of allogeneic HCT in indolent NHL are marked by substantial variation in eligibility criteria, patient populations, and transplant approach. Nonetheless, several common themes are apparent. Indolent NHL is highly susceptible to immunologic graft-versus-lymphoma effects and relapse rates after allogeneic HCT are uniformly low. Allogeneic HCT early in the disease course produces the highest overall and progression-free survival, but also increases patient exposure to potential transplant-related complications such as chronic graft-versus-host disease. In contrast, allogeneic HCT can be reserved as a 'last resort' for patients who are refractory to conventional chemotherapy, delaying their exposure to graft-versus-host disease and other transplant-associated risks. No trials have directly addressed the optimal timing of allogeneic HCT in indolent NHL nor prospectively compared different transplant approaches.
SUMMARY
Excellent outcomes have been reported with allogeneic HCT for indolent NHL, both early and late in the disease course. The optimal timing of allogeneic HCT is unknown and depends heavily on patient preferences.
Topics: Clinical Trials as Topic; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Transplantation Conditioning; Transplantation, Homologous
PubMed: 24104411
DOI: 10.1097/MOH.0b013e328365a151 -
Clinics in Chest Medicine Jun 2017This article reviews the noninfectious pulmonary syndromes that cause morbidity and mortality early after hematopoietic cell transplantation with an emphasis on risk... (Review)
Review
This article reviews the noninfectious pulmonary syndromes that cause morbidity and mortality early after hematopoietic cell transplantation with an emphasis on risk factors, clinical manifestations, treatment, and outcomes. The first section covers idiopathic pneumonia syndrome and its subtypes: peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, delayed pulmonary toxicity syndrome, and cryptogenic organizing pneumonia. The second section covers pulmonary toxicities of chemotherapies and immunosuppressive agents used in this setting. The final section covers less common syndromes, including pulmonary alveolar proteinosis, venous thromboembolism, pulmonary cytolytic thrombi, pulmonary venoocclusive disease, and transfusion-related acute lung injury.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Lung; Pneumonia; Risk Factors; Syndrome; Transplantation Conditioning
PubMed: 28477636
DOI: 10.1016/j.ccm.2016.12.007 -
Hematology. American Society of... Dec 2022Allogeneic hematopoietic stem cell transplantation is the treatment of choice for high-risk hematological malignancies such as acute myeloid and lymphocytic leukemia,...
Allogeneic hematopoietic stem cell transplantation is the treatment of choice for high-risk hematological malignancies such as acute myeloid and lymphocytic leukemia, myelodysplastic syndrome, and myeloproliferative disorders. Alternative donor transplantation from either haploidentical (haplo-SCT) or cord blood donor (CBT) is an established therapeutic alternative for patients who need transplants but lack a human leukocyte antigen-matched donor. Although haplo-SCT (mainly non-T-cell-depleted haplo-SCT with posttransplant cyclophosphamide) is increasing while CBT is decreasing worldwide (Figure 1), recent developments in CBT, especially cord blood expansion and other strategies to improve engraftment and immune reconstitution post-CBT, make CBT still a valuable option. This article discusses the 2 options based on the currently available data, focusing on adults, and tries to give some clues to help the transplant physician choose a haploidentical vs a cord blood donor. Given the limited numbers of published or ongoing well-designed randomized controlled trials comparing haplo-SCT to CBT and the overall similar clinical results in the available, mostly registry-based, and single-center studies, with substantial heterogeneity and variability, the decision to perform haplo-SCT or CBT in a given patient depends not only on the patient, disease, and donor characteristics and donor availability (although most if not all patients should have in principle an alternative donor) but also on the transplant physician's discretion and, most importantly, the center's experience and preference and ongoing protocols and strategies.
Topics: Adult; Humans; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Cord Blood Stem Cell Transplantation; Myelodysplastic Syndromes; Hematologic Neoplasms; Graft vs Host Disease; Unrelated Donors
PubMed: 36485156
DOI: 10.1182/hematology.2022000327 -
Cell Transplantation 2024While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first... (Review)
Review
While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first cell-based gene therapies for the treatment of patients 12 years of age and older with sickle cell disease (SCD), this treatment is not universally accessible. Allogeneic hematopoietic stem cell transplant (HSCT) has the potential to eradicate the symptoms of patients with SCD, but a significant obstacle in HSCT for SCD is the availability of suitable donors, particularly human leukocyte antigen (HLA)-matched related donors. Furthermore, individuals with SCD face an elevated risk of complications during stem cell transplantation due to SCD-related tissue damage, endothelial activation, and inflammation. Therefore, it is imperative to consider optimal conditioning regimens and investigate HSCT from alternative donors. This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and posttransplant outcomes.
Topics: Humans; Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning
PubMed: 38680015
DOI: 10.1177/09636897241246351 -
Stem Cells Translational Medicine Mar 2022Over the last decades, several studies demonstrated the possibility of lung regeneration through transplantation of various lung progenitor populations. Recently, we...
Over the last decades, several studies demonstrated the possibility of lung regeneration through transplantation of various lung progenitor populations. Recently, we showed in mice that fetal or adult lung progenitors could potentially provide donor cells for transplantation, provided that the lung stem cell niche in the recipient is vacated of endogenous lung progenitors by adequate conditioning. Accordingly, marked lung regeneration could be attained following i.v. infusion of a single cell suspension of lung cells into recipient mice conditioned with naphthalene (NA) and 6Gy total body irradiation (TBI). As clinical translation of this approach requires the use of allogenic donors, we more recently developed a novel transplantation modality based on co-infusion of hematopoietic and lung progenitors from the same donor. Thus, by virtue of hematopoietic chimerism, which leads to immune tolerance toward donor antigens, the lung progenitors can be successfully engrafted without any need for post-transplant immune suppression. In the present study, we demonstrate that it is possible to replace NA in the conditioning regimen with Cyclophosphamide (CY), approved for the treatment of many diseases and that a lower dose of 2 GY TBI can successfully enable engraftment of donor-derived hematopoietic and lung progenitors when CY is administered in 2 doses after the stem cell infusion. Taken together, our results suggest a feasible and relatively safe protocol that could potentially be translated to clinical transplantation of lung progenitors across major MHC barriers in patients with terminal lung diseases.
Topics: Animals; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Indicators and Reagents; Lung; Mice; Transplantation Chimera; Transplantation Conditioning
PubMed: 35298657
DOI: 10.1093/stcltm/szab016 -
Biology of Blood and Marrow... Apr 2015Over the last decade, the care of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has significantly improved, leading to a decrease in... (Review)
Review
Over the last decade, the care of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has significantly improved, leading to a decrease in deaths related to allo-HCT as well as improved long-term survival. However, for many patients, long-term survivorship is associated with a substantial burden of chronic morbidities. Indeed, malignant and nonmalignant late complications after allo-HCT are numerous and usually multifactorial, with all organs and tissues a potential target. In many cases, these long-term side effects are associated with the use of high-dose total body irradiation, myeloablative conditioning regimens, and the onset of chronic graft-versus-host disease. It appears to be essential to change the natural history of these late effects. This requires the introduction of improved conditioning regimens and the development of lifelong monitoring controls, patient counseling, and preventative treatment measures. This approach will allow us to pursue our efforts to improve patient outcome.
Topics: Allografts; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Survival Rate; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 25246296
DOI: 10.1016/j.bbmt.2014.09.010 -
Bone Marrow Transplantation Apr 2014With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to... (Review)
Review
With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.
Topics: Female; Fertility Preservation; Hematopoietic Stem Cell Transplantation; Humans; Male; Pregnancy; Transplantation Conditioning; Transplantation, Homologous
PubMed: 24419521
DOI: 10.1038/bmt.2013.211 -
Bone Marrow Transplantation Dec 2018Allogeneic hematopoietic cell transplantation (HCT) is the most established form of cancer immunotherapy and has been successfully applied for the treatment and cure of... (Review)
Review
Allogeneic hematopoietic cell transplantation (HCT) is the most established form of cancer immunotherapy and has been successfully applied for the treatment and cure of otherwise lethal neoplastic blood disorders. Cancer immune surveillance is mediated to a large extent by alloreactive T and natural killer (NK) cells recognizing genetic differences between patient and donor. Profound insights into the biology of these effector cells has been obtained over recent years and used for the development of innovative strategies for intelligent donor selection, aiming for improved graft-versus-leukemia effect without unmanageable graft-versus-host disease. The cellular composition of the stem cell source plays a major role in modulating these effects. This review summarizes the current state-of the-art of donor selection according to HLA, NK alloreactivity and stem cell source.
Topics: Donor Selection; Hematopoietic Stem Cell Transplantation; Recurrence; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous
PubMed: 29795435
DOI: 10.1038/s41409-018-0218-1 -
Journal of Korean Medical Science Jun 2021This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information...
BACKGROUND
This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR).
METHODS
We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000-September 2017) at our center.
RESULTS
Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97-28.0, < 0.001) and lower CD34⁺ cell dose (RR, 2.44-2.84, = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse.
CONCLUSION
Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.
Topics: Adolescent; Adult; Aged; Female; Graft Rejection; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Transplantation Conditioning; Transplantation, Homologous; Treatment Failure; Young Adult
PubMed: 34128593
DOI: 10.3346/jkms.2021.36.e151 -
Transplantation and Cellular Therapy Feb 2022Randomized clinical trials offer the highest-quality data for modifying clinical practice. Results of a phase III randomized trial of nonmyeloablative transplantation... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized clinical trials offer the highest-quality data for modifying clinical practice. Results of a phase III randomized trial of nonmyeloablative transplantation for adults with high-risk hematologic malignancies with 2 umbilical cord blood (UCB) units (n = 183) or HLA-haploidentical relative bone marrow (Haplo-BM; n = 154) revealed a 2-year progression-free survival (PFS) of 41% after Haplo-BM transplantation and 35% after 2-unit UCB transplantation (P = .41), with overall survival (OS) of 57% and 46%, respectively (P = .04). We sought to examine the generalizability of BMT CTN 1101 to a contemporaneous cohort beyond the trial's prespecified 2-year outcomes. All transplantations were performed between June 2012 and June 2018 in the United States. We hypothesized that the results of a rigorous phase III randomized trial would be generalizable. Changes in graft selection for HLA-haploidentical relative transplantation during the trial period allowed comparison of outcomes after transplantation with Haplo-BM with those after haploidentical peripheral blood (Haplo-PB). The trial's broad eligibility criteria were applied to the data source of the Center for International Blood and Marrow Transplant Research to select nontrial subjects. Extended follow-up of trial subjects was obtained from this data source. Three separate analyses were performed: (1) trial subjects beyond the trial's 2-year endpoint; (2) comparison of trial subjects with a contemporaneous cohort of nontrial subjects (195 2-unit UCB, 358 Haplo-BM, and 403 Haplo-PB); and (3) comparison of nontrial subjects by donor and graft type. Multivariate analyses were performed using Cox proportional hazards models for comparison of outcomes by treatment groups. With longer follow-up of the trial cohorts, 5-year PFS (37% versus 29%; P = .08) and OS (42% versus 36%; P = .06) were not significantly different between the treatment groups. We then compared the trial results with outcomes of comparable real-world transplantations. Five-year OS did not differ between trial and nontrial 2-unit UCB transplantations (36% versus 41%; P = .48) or between trial and nontrial Haplo-BM transplantations (42% versus 47%; P = .80), confirming generalizability. The randomized trial did not accrue as planned and therefore lacked the statistical power to detect a 15% difference in PFS. With substantially larger numbers of nontrial Haplo-BM transplantations, 5-year survival was higher after nontrial Haplo-BM compared with trial 2-unit UCB (47% versus 36%; P = .012). Nontrial patients who underwent Haplo-PB transplantation had higher 5-year survival (54%) compared with trial Haplo-BM (hazard ratio [HR], 0.76; P = .044) and nontrial Haplo-BM (HR, 0.78; P = .026). Similarly, survival was better after Haplo-PB compared with trial UCB (HR, 0.57; P < .0001) and nontrial UCB (HR, 0.63; P = .0002). When considering alternative donor low-intensity conditioning regimen transplantation, a haploidentical relative is preferred, and PB is the preferred graft source.
Topics: Adult; Fetal Blood; Graft vs Host Disease; Humans; Transplantation Conditioning; Transplantation, Haploidentical; Unrelated Donors
PubMed: 34775146
DOI: 10.1016/j.jtct.2021.11.002