Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical ...cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed.
Allogeneic hematopoietic cell transplant is a curative procedure for many patients with leukemia, lymphoma, myelodysplasia, myeloproliferative neoplasms, and genetic disorders. Umbilical cord blood ...transplantation is a graft source for patients who do not have a matched donor in their family or in the unrelated registry. It is particularly difficult for Black, Hispanic, and White patients of non-Western European background to find fully matched adult volunteer donors. An estimated 700,000 umbilical cord blood units have been donated for public use, and over 40,000 umbilical cord blood transplantations have been performed. Over 25,000 patients have been cured with this approach.
The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity ...conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).
MLL-Rearranged Acute Lymphoblastic Leukemia El Chaer, Firas; Keng, Michael; Ballen, Karen K.
Current hematologic malignancy reports,
04/2020, Letnik:
15, Številka:
2
Journal Article
Recenzirano
Purpose of Review
Rearrangements of the histone
lysine K-MethylTransferase 2A gene
(
KMT2A
) gene on chromosome 11q23, formerly known as the mixed-lineage leukemia (
MLL
) gene, are found in 10% and ...5% of adult and children ALL cases, respectively. The most common translocated genes are
AFF1
(formerly
AF4
),
MLLT3
(formerly
AF9
), and
MLLT1
(formerly
ENL
). The bimodal incidence of
MLL
-r-ALL usually peaks in infants in their first 2 years of life and then declines thereafter during the pediatric/young adult phase until it increases again with age.
MLL
-rearranged ALL (
MLL
-r-ALL) is characterized by hyperleukocytosis, aggressive behavior with early relapse, relatively high incidence of central nervous system (CNS) involvement, and poor prognosis.
Recent Findings
MLL
-r-ALL cells are characterized by relative resistance to corticosteroids (due to Src kinase-induced phosphorylation of annexin A2) and L-asparaginase therapy, but they are sensitive to cytarabine chemotherapy (due to increased levels of
hENT1
expression). Potential therapeutic targets include FLT3 inhibitors, MEK inhibitors, HDAC inhibitors, BCL-2 inhibitors, MCL-1 inhibitors, proteasome inhibitors, hypomethylating agents, Dot1L inhibitors, and CDK inhibitors.
Summary
In this review, we discuss
MLL
-r-ALL focusing on clinical presentation, risk stratification, drug resistance, and treatment strategies, including potential novel therapeutic targets.
Only 30% of patients who require an allogeneic hematopoietic cell transplant will have an HLA-matched sibling donor. A search for an unrelated donor will be undertaken for patients without a matched ...family donor. However, many patients, particularly patients of diverse racial and ethnic backgrounds, may not be able to rapidly identify a suitably matched unrelated donor. Three alternative graft sources, umbilical cord blood (UCB), haploidentical (haplo)–related donor, and mismatched unrelated donor (MMUD) are available. UCB is associated with decreased GVHD, but hematologic recovery and immune reconstitution are slow. Haplo-HCT is characterized by donor availability for transplantation and after transplantation adoptive cellular immunotherapy but may be complicated by a high risk of graft failure and relapse. A MMUD transplant may also be an option, but GVHD may be of greater concern. Phase 2 studies have documented advances in HLA typing, GVHD prophylaxis, and infection prevention, which have improved survival. The same patient evaluated in different transplant centers may be offered MMUD, UCB, or haplo-HCT depending on center preference. In this review, we discuss the rationale for donor choice and the need of phase 3 studies to help answer this important question.
T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive hematologic malignancy with a poor prognosis. Alemtuzumab (Campath) remains the cornerstone for treatment, with an 80% complete response ...(CR). Hematopoietic stem cell transplant (HSCT) is considered the standard of care as consolidative therapy in eligible patients. However, allogeneic stem cell transplant is also complicated by increased rates of infections from chemotherapy, acute graft-versus-host disease (GVHD), and chronic GVHD. This review aims to report the available literature on the efficacy and complications of consolidative HSCT. It also discusses the importance of patient selection and pre- and post-transplant complications including atypical infections and GVHD.
Cord blood transplant for acute myeloid leukaemia Ballen, Karen K.; Lazarus, Hillard
British journal of haematology,
April 2016, 2016-Apr, 2016-04-00, 20160401, Letnik:
173, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Umbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia (AML), other haematological malignancies and metabolic diseases who can be cured by ...allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first cord blood transplants were done in children, there are currently more cord blood transplants performed in adults. In this review, we explore the history of umbilical cord blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical cord blood transplantation cures approximately 30–40% of adults and 60–70% of children with AML. Controversial issues, including the use of double versus single cord blood units for transplantation, optimal cord blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed.
Since the first report of a successful umbilical cord blood transplantation in 1988, there has been great interest in the use of cord blood as an alternative stem cell source to treat cancer and ...genetic diseases. More than 4000 cord blood transplantations have been performed worldwide. In this review, the scientific rationale for this therapy, as well as related preclinical studies, cord blood banking issues, and ethical concerns, will be addressed. Results of studies in both pediatric and adult transplantation will be discussed. Finally, new indications for cord blood use and emerging technologies will be addressed.
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