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Neuro-oncology Oct 2017Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a...
BACKGROUND
Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy.
METHODS
Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 × 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day × 3 days, then busulfan 3.2 mg/kg/day × 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing.
RESULTS
Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors.
CONCLUSIONS
TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odg_msk_2017, accessed 6 January 2017.
CLINICALTRIALS.GOV REGISTRY
NCT00588523.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Dacarbazine; Disease-Free Survival; Female; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Oligodendroglioma; Stem Cell Transplantation; Temozolomide; Transplantation, Autologous
PubMed: 28472509
DOI: 10.1093/neuonc/nox086 -
Orphanet Journal of Rare Diseases Oct 2014Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases... (Review)
Review
Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins... Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease Management; Endocrine System Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hormone Replacement Therapy; Humans; Metabolic Diseases
PubMed: 25496809
DOI: 10.1186/s13023-014-0162-0 -
British Journal of Haematology Sep 2006Improvements in survival in adult acute myeloid leukaemia (AML) have yet to be gleaned from either refinements in the understanding of the pathophysiology of the disease... (Review)
Review
Improvements in survival in adult acute myeloid leukaemia (AML) have yet to be gleaned from either refinements in the understanding of the pathophysiology of the disease or from the expanding pool of targeted therapies. Outcomes have remained particularly dismal in older patients. Ongoing and planned trials will assess the effects of drugs targeting biological pathways whose clinical importance may vary as a function of the unique genotype and phenotype of each case of AML. The success of these ventures will ultimately require well-designed clinical trials in subsets of patients with risk being dependent not only on age and cytogenetics, but on additional, increasingly quantifiable biological variables. Inhibitors of fms-like tyrosine kinase-3, farnesyl transferase, apoptotic and angiogenic pathways are being studied alone and in combination with chemotherapy. Biological therapies, including monoclonal antibodies, peptide vaccines and interleukin-2, are undergoing evaluation. The role of autologous as well as allogeneic myeloablative and reduced-intensity transplantation continues to be defined. Several potentially useful new cytotoxic agents are being introduced. Critically important to advancing the field in light of such an increasing number of choices is a reassessment of traditional phase II trial designs so that more efficient evaluation of new therapies may take place, even as well-designed phase III trials continue to be performed.
Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Humans; Immunotherapy; Leukemia, Myeloid; Prognosis; Remission Induction
PubMed: 16848792
DOI: 10.1111/j.1365-2141.2006.06219.x -
Romanian Journal of Ophthalmology 2021Globe salvage marks the treatment success of retinoblastoma. To evaluate four treatment strategies in group D and group E retinoblastoma. Retrospective case series in...
Globe salvage marks the treatment success of retinoblastoma. To evaluate four treatment strategies in group D and group E retinoblastoma. Retrospective case series in a tertiary hospital. 81 patients with Group D and Group E retinoblastoma. Participants were divided into four sets. In set I, eyes received primary intravenous chemotherapy (IVC), cryotherapy (CT), laser therapy (LT) and Intravitreal Chemotherapy with Melphalan (IViC). In set II, primary IVC was combined with second line IVC, CT, LT and IVT-M. Set III eyes received primary IVC and Intra-arterial chemotherapy (IAC), CT, LT and IViC. Set IV eyes received IAC, CT, LT and IViC. Treatment failure was defined as inadequate response during or after IVC or IAC. globe salvage and enucleation rates. 52 eyes were included in group D and 29 in group E. In group D, globe salvage was obtained in 8 out of 11 eyes in Set I, 13 out of 19 eyes in set II, 5 out 6 eyes in set III, and 13 out of 16 eyes in set IV. In group E, enucleation was performed in 17 eyes. Global salvage was obtained in 0 out of 2 eyes in set I, 2 out of 3 eyes in set II, 3 out of 5 in set III, and in 1 out of 2 eyes in set IV. IVC with adjuvant IAC, LT, CT and IViC has shown favorable results as a treatment method for group D and group E retinoblastoma.
Topics: Adult; Combined Modality Therapy; Cryotherapy; Eye Enucleation; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Melphalan; Myeloablative Agonists; Neoplasm Staging; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 33817429
DOI: 10.22336/rjo.2021.5 -
Pediatric Blood & Cancer Dec 2008Children and adolescents with malignant astrocytomas recurring after initial treatment have a dismal prognosis, with only rare patients surviving 1-year beyond... (Comparative Study)
Comparative Study
Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma: outcome compared with conventional chemotherapy: a report from the Children's Oncology Group.
PURPOSE
Children and adolescents with malignant astrocytomas recurring after initial treatment have a dismal prognosis, with only rare patients surviving 1-year beyond recurrence. The purpose of this study was to attempt to improve their survival.
METHODS
Twenty-seven children and adolescents with malignant astrocytomas [17 glioblastoma multiforme and 10 anaplastic astrocytoma (AA)] following initial tumor progression, received myeloablative chemotherapy followed by autologous marrow rescue with one of three thiotepa and etoposide-based chemotherapy regimens, administered alone (n = 11) or combined with carmustine (n = 5) or carboplatin (n = 11). Time to progression and death following myeloablative chemotherapy for these patients was compared non-randomly with outcome of a contemporaneously treated cohort of similar patients who received only conventional chemotherapy following initial tumor progression. The two cohorts were compared for age, histology, prior therapies, extent of surgical resection at progression, and time from initial diagnosis to progression.
RESULTS
Five of 27 children (two with glioblastoma multiforme and three with AA) survive event-free from 8.3 to 13.3 years (median of 11.1 years) following myeloablative chemotherapy. Of 56 children with recurrent malignant astrocytoma who received conventional chemotherapy following initial progression, no patient survives. Differences in distributions of survival were not significant when stratified by surgical debulking (P = 0.39). However, for patients who were surgically debulked, the survival distributions are significantly different (P = 0.017).
CONCLUSIONS
Myeloablative chemotherapy with autologous marrow rescue can produce durable remissions in children and young adults with recurrent malignant gliomas, in the setting of minimal residual tumor burden achieved surgically.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Bone Marrow Transplantation; Brain Neoplasms; Carboplatin; Carmustine; Child; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Etoposide; Female; Humans; Infant; Male; Myeloablative Agonists; Neoplasm Recurrence, Local; Prognosis; Salvage Therapy; Thiotepa; Transplantation, Autologous
PubMed: 18802947
DOI: 10.1002/pbc.21732 -
Annals of Oncology : Official Journal... Aug 2002There is a clear rationale for using hyperthermia in cancer treatment. Treatment at temperatures between 40 and 44 degrees C is cytotoxic for cells in an environment... (Review)
Review
There is a clear rationale for using hyperthermia in cancer treatment. Treatment at temperatures between 40 and 44 degrees C is cytotoxic for cells in an environment with a low pO(2) and low pH, conditions that are found specifically within tumour tissue, due to insufficient blood perfusion. Under such conditions radiotherapy is less effective, and systemically applied cytotoxic agents will reach such areas in lower concentrations than in well perfused areas. Therefore, the addition of hyperthermia to radiotherapy or chemotherapy will result in at least an additive effect. Furthermore, the effects of both radiotherapy and many drugs are enhanced at an increased temperature. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, regional hyperthermia by perfusion of organs or limbs, or by irrigation of body cavities, and whole body hyperthermia. The use of hyperthermia alone has resulted in complete overall response rates of 13%. The clinical value of hyperthermia in addition to other treatment modalities has been shown in randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, vulva and vagina, and also for melanoma. Additional hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects and/or better overall survival rates. Generally, when combined with radiotherapy, no increase in radiation toxicity could be demonstrated. Whether toxicity from chemotherapy is enhanced depends on sequence of the two modalities, and on which tissues are heated. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. Recent developments include improvements in heating techniques and thermometry, development of hyperthermia treatment planning models, studies on heat shock proteins and an effect on anti-cancer immune responses, drug targeting to tumours, bone marrow purging, combination with drugs targeting tumour vasculature, and the role of hyperthermia in gene therapy. The clinical results achieved to date have confirmed the expectations raised by results from experimental studies. These findings justify using hyperthermia as part of standard treatment in tumour sites for which its efficacy has been proven and, furthermore, to initiate new studies with other tumours. Hyperthermia is certainly a promising approach and deserves more attention than it has received until now.
Topics: Antineoplastic Agents; Body Temperature; Clinical Trials as Topic; Combined Modality Therapy; Humans; Hyperthermia, Induced; Neoplasms
PubMed: 12181239
DOI: 10.1093/annonc/mdf280 -
Experimental Hematology Mar 2001Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and... (Review)
Review
Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD. Afferent phase of acute GVHD starts with myeloablative conditioning, i.e., before the infusion of the graft. Total-body irradiation (TBI) or high-dose chemotherapy regimens cause extensive damage and activation in host tissues, which release inflammatory cytokines and enhance recipient major histocompatibility complex (MHC) antigens. Recognition of the foreign host antigens by donor T cells and activation, stimulation, and proliferation of T cells is crucial in the afferent phase. Effector phase of acute GVHD results in direct and indirect damage to host cells. The skin, gastrointestinal tract, and liver are major target organs of acute GVHD. Combination drug prophylaxis in GVHD is essential in all patients undergoing allogeneic HSCT. Steroids have remained the standard for the treatment of acute GVHD. Several clinical trials have evaluated monoclonal antibodies or receptor antagonist therapy for steroid-resistant acute GVHD, with different successes in a variety of settings. There are some newer promising agents like mycophenolate mofetil, glutamic acid-lysine-alanine-tyrosine (GLAT), rapamycin, and trimetrexate currently entering in the clinical studies, and other agents are in development. Future experimental and clinical studies on GVHD will shed further light on the better understanding of the disease pathobiology and generate the tools to treat malignant disorders with allogeneic HSCT with specific graft-vs-tumor effects devoid of GVHD.
Topics: Acute Disease; Animals; Antibodies, Monoclonal; Antigen Presentation; Antineoplastic Agents; Bone Marrow; Digestive System; Dogs; Drug Design; Drug Therapy, Combination; Forecasting; Graft vs Host Disease; HLA Antigens; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Liver; Lymphocyte Depletion; Lymphokines; Mice; Models, Biological; Premedication; Radiation Chimera; Radiation Injuries; Randomized Controlled Trials as Topic; Receptors, Interleukin-2; Risk Factors; Severity of Illness Index; Skin; T-Lymphocytes, Cytotoxic; Transplantation Conditioning; Transplantation, Homologous; Whole-Body Irradiation
PubMed: 11274753
DOI: 10.1016/s0301-472x(00)00677-9 -
Biology of Blood and Marrow... May 2016It was previously postulated that pretransplant myeloablative treatment may impair thymopoiesis, contributing in this way to delayed reconstitution of T cells after... (Comparative Study)
Comparative Study
It was previously postulated that pretransplant myeloablative treatment may impair thymopoiesis, contributing in this way to delayed reconstitution of T cells after hematopoietic stem cell transplantation (HSCT). On the other hand, de novo generation of T cells after HSCT requires a competent thymus. Various myeloablative conditioning regimens (total body irradiation [TBI] or high-dose chemotherapy) routinely used in clinical practice may have potentially different impacts on the thymus. However, no comparative study on thymic output and T cell repertoire in autologous (auto)HSCT model has been presented so far. Here we evaluated thymic output and TCR diversity in 45 lymphoma patients submitted to autoHSCT differing in respect to conditioning regimen: high-dose chemotherapy as monotherapy (BEAM, n = 22) or combination of total body irradiation with cyclophosphamide chemotherapy: Cy/TBI (n = 23). Thymic output was assessed before and on days +100, +180, and +365 after autoHSCT by flow cytometric counts of recent thymic emigrant (RTE) cells (CD31(+) CD62L(+) CD45RA(+) CD4(+)) and quantification of signal joint TCR receptor excision circles (sjTRECs) by quantitative PCR. T cell repertoire diversity was analyzed on day +365 after autoHSCT by spectra-typing of the CDR3 region in the TCRVβ chain. The BEAM group, in contrast to the Cy/TBI group, manifested significantly higher proportions of RTE cells and sjTREC copy numbers on days +100 and +180. Analysis of TCRVβ spectra-types on day +365 revealed more restricted (monoclonal or oligoclonal) T cell repertoires in the Cy/TBI versus BEAM group (48.8% versus 18.2%, P = .0002). In conclusion, the conditioning scheme based on BEAM chemotherapy may be performed with lower risk of thymic destruction and T cell repertoire distortion than Cy/TBI scheme. This finding may help to potentially improve conditioning schemes to efficiently perform myeloablation and maintain active thymopoiesis.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Autografts; Carmustine; Cyclophosphamide; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Podophyllotoxin; Thymus Gland; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 26797400
DOI: 10.1016/j.bbmt.2016.01.014 -
The Cochrane Database of Systematic... Oct 2015Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence. High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival. This review is the second update of a previously published Cochrane review.
OBJECTIVES
Primary objectiveTo compare the efficacy, that is event-free and overall survival, of high-dose chemotherapy and autologous bone marrow or stem cell rescue with conventional therapy in children with high-risk neuroblastoma. Secondary objectivesTo determine adverse effects (e.g. veno-occlusive disease of the liver) and late effects (e.g. endocrine disorders or secondary malignancies) related to the procedure and possible effects of these procedures on quality of life.
SEARCH METHODS
We searched the electronic databases The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, issue 11), MEDLINE/PubMed (1966 to December 2014) and EMBASE/Ovid (1980 to December 2014). In addition, we searched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2002 to 2014), American Society for Pediatric Hematology and Oncology (ASPHO) (from 2002 to 2014), Advances in Neuroblastoma Research (ANR) (from 2002 to 2014) and American Society for Clinical Oncology (ASCO) (from 2008 to 2014). We searched for ongoing trials by scanning the ISRCTN register (www.isrct.com) and the National Institute of Health Register (www.clinicaltrials.gov). Both registers were screened in April 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing the efficacy of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients.
DATA COLLECTION AND ANALYSIS
Two authors independently performed study selection, data extraction and risk of bias assessment. If appropriate, we pooled studies. The risk ratio (RR) and 95% confidence interval (CI) was calculated for dichotomous outcomes. For the assessment of survival data, we calculated the hazard ratio (HR) and 95% CI. We used Parmar's method if hazard ratios were not reported in the study. We used a random-effects model.
MAIN RESULTS
We identified three RCTs including 739 children. They all used an age of one year as the cut-off point for pre-treatment risk stratification. The first updated search identified a manuscript reporting additional follow-up data for one of these RCTs, while the second update identified an erratum of this study. There was a significant statistical difference in event-free survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (three studies, 739 patients; HR 0.78, 95% CI 0.67 to 0.90). There was a significant statistical difference in overall survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (two studies, 360 patients; HR 0.74, 95% CI 0.57 to 0.98). However, when additional follow-up data were included in the analyses the difference in event-free survival remained statistically significant (three studies, 739 patients; HR 0.79, 95% CI 0.70 to 0.90), but the difference in overall survival was no longer statistically significant (two studies, 360 patients; HR 0.86, 95% CI 0.73 to 1.01). The meta-analysis of secondary malignant disease and treatment-related death did not show any significant statistical differences between the treatment groups. Data from one study (379 patients) showed a significantly higher incidence of renal effects, interstitial pneumonitis and veno-occlusive disease in the myeloablative group compared to conventional chemotherapy, whereas for serious infections and sepsis no significant difference between the treatment groups was identified. No information on quality of life was reported. In the individual studies we evaluated different subgroups, but the results were not univocal in all studies. All studies had some methodological limitations.
AUTHORS' CONCLUSIONS
Based on the currently available evidence, myeloablative therapy seems to work in terms of event-free survival. For overall survival there is currently no evidence of effect when additional follow-up data are included. No definitive conclusions can be made regarding adverse effects and quality of life, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (e.g. stage of disease and patient age) and have a long-term follow-up. Different risk groups, using the most recent definitions, should be taken into account.It should be kept in mind that recently the age cut-off for high risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease have been included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Infant; Neoplasm Recurrence, Local; Neuroblastoma; Prognosis; Randomized Controlled Trials as Topic; Salvage Therapy
PubMed: 26436598
DOI: 10.1002/14651858.CD006301.pub4 -
Journal of Clinical Immunology May 2022Current treatment for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) includes enzyme replacement therapy (ERT), allogeneic hematopoietic...
Current treatment for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) includes enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplant (HSCT), or ex vivo corrected autologous hematopoietic stem cell gene therapy. Historic data show HSCT survival is superior using unconditioned matched sibling and family compared to matched unrelated and haploidentical donors. Recent improvement in HSCT outcomes prompted us to retrospectively examine HSCT survival and long-term graft function in ADA-SCID transplanted at our center. Thirty-three ADA-deficient patients received HSCT between 1989 and 2020, with follow-up data to January 2021. Chemotherapy conditioning regimens were defined as myeloablative (MAC-busulfan/cyclophosphamide), reduced-toxicity myeloablative (RT-MAC-treosulfan-based, since 2007), or no conditioning. Serotherapy used included alemtuzumab (with or without other conditioning agents) or antithymocyte globulin (ATG). ERT was introduced routinely in 2010 until commencement of conditioning. Median age at HSCT was 3.2 (0.8-99.8) months. Twenty-one (63.6%) received stem cells from unrelated or haploidentical donors. Seventeen (51.5%) received chemotherapy conditioning and 16 (48.5%) received alemtuzumab. Median follow-up was 7.5 (0.8-25.0) years. Overall survival (OS) and event-free survival (EFS) at 8 years were 90.9% (95% CI: 79.7-100.0%) and 79% (55-91%), respectively. OS after 2007 (n = 21) was 100% vs 75% before 2007 (n = 12) (p = 0.02). Three (9.1%) died after HSCT: two from multiorgan failure and one from unexplained encephalopathy. There were no deaths after 2007, among those who received ERT and treosulfan-based conditioning pre-HSCT. Ten (30.3%) developed acute GvDH (3 grade II, 2 grade III); no chronic GvHD was observed. In the modern era, conditioned HSCT with MUD has a favorable outcome for ADA-deficient patients.
Topics: Adenosine Deaminase; Agammaglobulinemia; Alemtuzumab; Enzyme Replacement Therapy; Genetic Therapy; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Severe Combined Immunodeficiency; Transplantation Conditioning
PubMed: 35288820
DOI: 10.1007/s10875-022-01238-0