The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases.Median number of nucleated cells infused was 1.71 ؋ 10 7 /kg (range, 1.01 ؋ 10 7 /kg to 4.96 ؋ 10 7 /kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 ؋ 10 9 /L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 ؋ 10 9 /L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients.Twelve patients remained alive and diseasefree 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P ؍ .01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor. (Blood. 2001;98:2332-2338)
BackgroundDespite the prophylactic use of allopurinol, tumor lysis syndrome (TLS)-related morbidity and mortality still occur in a number of patients with acute myeloid leukemia (AML). The aim of this study was: (i) to analyze the incidence and outcome of TLS in a large series of patients with AML receiving hyperhydration and allopurinol, (ii) to identify risk factors for TLS, and (iii) to develop a prognostic scoring system for estimating individual risk of TLS.
Clinical studies focused on disease-specific outcomes of cord blood transplant (CBT) from unrelated donors are limited. We analyzed the outcome and prognostic factors of 49 adults with high-risk acute myelogenous leukemia (AML) receiving single-unit CBT from unrelated donors after myeloablative (MA) conditioning at a single institution. Conditioning regimens were based on the combination of thiotepa, busulfan (Bu), cyclophospamide (Cy), or fludarabine (Flu), and antithymocyte globulin (ATG). Cumulative incidence of myeloid and platelet engraftment was 96% and 73% at a median time of 20 and 62 days, respectively. Engraftment was significantly faster for patients receiving higher doses of CD34(+) cells. Confidence Interval of graft-versus-host disease (GVHD), acute GVHD (aGVHD) grade II-IV, III-IV, and extensive chronic GVHD (cGVHD) were 26%, 15%, and 30%, respectively. Leukemia-free survival (LFS), nonrelapse mortality (NRM), and relapse at 2 years were 42%, 39%, and 19%, respectively. Low number of total nucleated cells (TNC) had a negative impact on NRM and LFS. Patients transplanted in first complete remission (CR1) receiving TNC above 2 x 10(7)/kg had a 4-year LFS of 75%. These results show that CBT from unrelated donors is a curative treatment for a substantial number of patients with high-risk AML, particularly if transplant is performed with highly cellular units in patients in first CR.
Summary:Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16-46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gramnegative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT. Bone Marrow Transplantation (2002) 30, 937-943.
Chromosomal translocations in hematological malignancies often result in novel fusion chimeric genes. We report a case of acute myeloid leukemia with a clonal translocation t(11;12)(p15;q13) display- IntroductionChromosomal translocations in hematological malignancies often result in the generation of novel chimeric genes. The nucleoporin 98 gene (NUP98) located at chromosome 11p15 is recurrently involved in a variety of rearrangements in both myeloid and lymphoid malignancies. 1,2 After the first NUP98 rearrangement, Homeobox A9 gene (NUP98/HOXA9), was discovered, more than 20 different fusion partners were reported. 1 Among these partners, other homeobox and non-homeobox genes have been identified as fusion partners of NUP98. We report here a novel NUP98 rearrangement in a patient with acute myeloid leukemia displaying morphologic and immunophenotypic features resembling the classical hypergranular subtype of acute promyelocytic leukemia. This case harbored a novel fusion gene as a result of a chromosomal break point at 12q13 detected in a new 11p15 rearrangement. The gene fused to NUP98 was identified by comparative genomic hybridization (CGH) array as the retinoid acid receptor gamma gene (RARG). RARG is a member of the nuclear receptor superfamily and shares high homology (90%) with RARA and RARB, the other retinoic acid receptors that are involved in retinoid signaling. While an artificial construct has been reported in which RARG is fused to the promyelocytic leukemia gene product (PML), resulting in an oncogenic protein, 3 no cases of human leukemia-bearing RARG fusions have been described. Methods Case reportsThis study was approved by the institutional review board of the Hospital Universitario La Fe. A 35-year-old man was referred to our department with asthenia, mucosal bleeding, spontaneous ecchymoses, and fever. Blood tests showed a hemoglobin level of 6 g/dL, a platelet count of 8 ϫ 10 9 /L, and a white blood cell count of 12 ϫ 10 9 /L with 82% blasts and atypical promyelocytes. Although increased levels of D-dimer were present, the patient did not fulfill the criteria for coagulopathy. 4 Morphologic examination of bone marrow (BM) smears disclosed a monomorphic infiltration by blast cells, 80% hypergranular (atypical promyelocytes, which frequently displayed Auer rods) resembling the hypergranular subtype of acute promyelocytic leukemia (M3) of the French-American-British classification ( Figure 1A-B). The immunophenotype of peripheral blood blasts was positive for CD13, CD33, CD45, CD117, and cMPO, weakly positive for CD34, and negative for HLA-DR and B-cell and T-cell markers. The immunofluorescence staining with the anti-PML monoclonal antibody (PG-M3) 5 was negative in both BM and peripheral blood samples. Moreover, reverse transcription polymerase chain reaction (RT-PCR) to amplify the PML/RARA fusion gene and conventional karyotyping to search for the t(15;17) were also negative. Due to the clinical suspicion of acute promyelocytic leukemia, the patient was started on all-trans retinoic ac...
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