- N Engl J Med 2022; 387:132-147
In a large, multinational, randomized trial, continuous lenalidomide maintenance therapy after triplet therapy (lenalidomide, bortezomib, and dexamethasone) and autologous stem-cell transplantation resulted in longer progression-free survival than triplet therapy alone.
- N Engl J Med 2022; 386:2508-2516
A 25-year-old man with a history of leukemia and hematopoietic-cell transplantation was evaluated for vision changes. MRI revealed white-matter lesions; PET-CT showed FDG-avid lymphadenopathy. A diagnostic test was performed.
- N Engl J Med 2022; 386:2295-2302
Three patients with Schimke immuno-osseous dysplasia who underwent sequential bone marrow and kidney transplantation continued to have normal renal function without immunosuppression at 22 to 34 months.
- N Engl J Med 2022; 386:2332-2333
Stunning advances in human transplantation have been tempered by the immunologic consequences of histoincompatibility between donor and recipient — namely, allograft rejection after solid-organ transplantation and graft-versus-host disease (GVHD) after hematopoietic stem-cell (bone marrow) transplantation (HSCT). The separation of GVHD from the graft-versus-tumor effect and the induction of functional immune...
- N Engl J Med 2022; 386:2145-2148
This explanatory editorial elucidates the components and concepts behind a study, described in this issue of the Journal, that involves therapeutic targeting of pancreatic cancer with an autologous T cell engineered to have exquisite specificity for targeting the cancer cell.
- N Engl J Med 2022; 386:2143-2144
Pancreatic ductal adenocarcinoma is the deadliest of all common cancers. The reasons for this are the advanced cancer stage by the time symptoms are noted and the occult presence of micrometastases in the liver and elsewhere at the time of initial surgical treatment. In addition, systemic therapy with chemotherapy rarely...
- N Engl J Med 2022; 386:2112-2119
A 71-year-old woman with progressive pancreatic adenocarcinoma containing a mutated KRAS oncogene was given adoptive cellular therapy of her own T cells that had been altered to express two different T-cell receptors specific for her HLA type and the mutated KRAS in the tumor. Six months...
- N Engl J Med 2022; 386:629-639
A randomized trial comparing the CD19-specific CAR T-cell therapy tisagenlecleucel with salvage chemotherapy followed by high-dose therapy and autologous hematopoietic stem-cell transplantation in patients with refractory or early relapsed aggressive B-cell lymphoma did not show a longer event-free survival with CAR T cells.
- N Engl J Med 2022; 386:640-654
In a trial involving patients with relapsed or refractory large B-cell lymphoma, the CAR T-cell therapy axicabtagene ciloleucel led to significantly longer event-free survival than standard salvage chemotherapy (which was followed by high-dose therapy and autologous stem-cell transplantation in patients with a response). High-grade toxic effects were common, but most...
- N Engl J Med 2022; 386:692-696
Large B-cell lymphoma is a spectrum of aggressive B-cell cancers with broad genetic and clinical heterogeneity.1 First-line chemotherapy cures most patients, but those with relapsed or refractory disease usually die of lymphoma. Salvage chemotherapy followed by autologous stem-cell transplantation (ASCT) is the standard second-line approach to large B-cell...
- N Engl J Med 2022; 386:488-490
β-Thalassemia results from insufficient production of the hemoglobin subunit β-globin (β+) or from the absence of β-globin (β0). Low levels of adult hemoglobin (HbA, or α2β2 ) are exacerbated by excess free α-globin chains in erythroid cells, leading to dyserythropoiesis and shortening red-cell...
- N Engl J Med 2022; 386:415-427
Of 23 patients with transfusion-dependent β-thalassemia who received gene-transfected autologous hematopoietic cells, 91% became transfusion independent; the remaining 2 patients had a low level of engraftment of vector-expressing cells. With a median of 29.5 months of follow-up, the average hemoglobin level was 11.7 g per deciliter.
- N Engl J Med 2021; 385:1929-1940
Eight patients with Hurler syndrome who lacked suitable allogeneic donors received autologous hematopoietic stem and progenitor cells transduced ex vivo with an α-L-iduronidase–encoding lentiviral vector. This therapy resulted in extensive metabolic correction in peripheral tissues and the central nervous system.
- N Engl J Med 2021; 385:1511-1520
A 21-year-old man with sickle cell trait presented with sore throat, epistaxis, and petechiae of the oropharynx. The hemoglobin level was 9.8 g per deciliter, the platelet count 1000 per microliter, and the white-cell count 670 per microliter. A test for SARS-CoV-2 RNA was positive. A diagnostic test was performed.
- N Engl J Med 2021; 385:921-929
A young man with a germline mutation in IL2RG had a history of herpes-related encephalitis and multiple skin and mucosal lesions caused by human papillomavirus, including a recurrent refractory nasal squamous-cell carcinoma. Allogeneic hematopoietic-cell transplantation resulted in clearing of the HPV lesions, including the nasal carcinoma.
- N Engl J Med 2021; 385:834-843
A 49-year-old man was evaluated because of relapsed acute myeloid leukemia that occurred 14 months after the initial diagnosis and treatment. Molecular genetic profiling at the time of relapse identified a new internal tandem duplication mutation in FLT3 (FLT3 -ITD). A bone marrow biopsy was performed, and...
- N Engl J Med 2021; 385:228-238
Standard treatment for GVHD is glucocorticoids, but for glucocorticoid-refractory GVHD, no intervention has emerged as standard second-line treatment. This trial with 329 patients compared ruxolitinib with control (chosen from among 10 possible therapies) in patients with glucocorticoid-refractory chronic GVHD. Response at week 24 was 50% with ruxolitinib as compared with...
- N Engl J Med 2021; 384:2451-2452
Some patients with acute leukemia or myelodysplastic syndromes with thrombocytopenia may become resistant to random donor transfusions of platelets and require HLA-matched platelets to have an adequate response. In one large center, the use of leukoreduction and universal ABO matching reduced the requirement for HLA-matched platelets from 12.5% to 0.4%...
- N Engl J Med 2021; 384:2002-2013
Fifty patients in the United States and the United Kingdom underwent HSCT with CD34+ cells transduced with a replication-defective lentivirus bearing ADA . At 24 months, all the patients were alive, and event-free survival was 96.7% among the U.S. patients and 95% among the U.K. patients. Only two patients...
- N Engl J Med 2021; 384:1942-1942
A 31-year-old man with refractory acute myeloid leukemia presented with worsening pain due to known spinal involvement of the leukemia. The white-cell count was 91,100 per cubic millimeter, and a peripheral-blood smear showed multiple mitotic and apoptotic figures.