T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive post-thymic malignancy with poor response to conventional treatment and short survival. It can readily be distinguished from other T-cell leukemias on the basis of the distinctive morphology, immunophenotype, and cytogenetics. Consistent chromosomal translocations involving the T-cell receptor gene and one of two protooncogenes (TCL-1 and MTCP-1) are seen in the majority of cases and are likely to be involved in the pathogenesis of the disorder. The CD52 antigen is expressed at high density on the malignant T-cells and therapy with alemtuzumab, a humanized IgG1 antibody that targets this antigen, has produced promising results. In relapsed/refractory patients overall and complete response rates have been seen in up to 76% and 60%, respectively. In previously untreated patients, complete remission rates of 100% have been reported. These responses are durable and translate into improved survival for responders. However, relapse is inevitable and strategies using both autologous and allogeneic stem cell transplantation are currently being explored. Additional clinical trials are investigating the use of alemtuzumab in combinations with chemotherapy, either concurrent or sequential. In the future we hope to have a better understanding of how best to integrate these therapeutic approaches to further prolong survival for patients with T-PLL.     

T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia is a rare post-thymic lymphoid disorder, which has distinctive clinical, morphologic, immunophenotypic and cytogenetic features. It has previously been associated with an aggressive course, poor response to conventional chemotherapy and a short median survival. Treatment with purine analogs and the monoclonal antibody alemtuzumab has resulted in significantly higher response rates and increased survival. However, responses are transient and allogeneic hematopoietic progenitor-cell transplantation remains the only potential curative option. The proportion of patients eligible for transplant is low, owing to the older age group of patients, and nonmyeloablative transplantation is a promising alternative that needs to be explored.     

非血缘脐血造血干细胞移植的现状

 脐血是骨髓和外周血干细胞以外的新的干细胞主要来源,脐血移植特别是非血缘脐血移植（UCBT）的数量逐年增加。UCBT存在的主要问题在于脐血的造血干／祖细胞（HSC／HPC）数量少,可能导致植入延迟或植入失败。临床上采用多种方法来提高脐血HSC／HPC的数量,包括双份脐血输注、减低强度的预处理、体内体外扩增脐血细胞、同时输注单倍体血缘供者CD+34细胞或间充质干细胞（MSC）、或将脐血细胞直接注入骨髓等,取得了良好的疗效。UCBT将会成为更多患者的治疗选择。     

单倍体造血干细胞联合脐血输注治疗白血病的临床研究

目的 分析单倍体造血干细胞联合第三方脐血输注治疗白血病的疗效及安全性.方法 对苏州大学附属第一医院2011年1月至2012年5月44例采用单倍体造血干细胞联合第三方脐血输注治疗的白血病患者进行回顾性分析,其中急性淋巴细胞白血病（ALL） 16例、急性髓系白血病（AML）24例、慢性粒细胞白血病（CML）3例、T淋巴母细胞淋巴瘤1例.结果 44例白血病患者回输的单倍体供体移植物中CD34＋细胞中位数为3.14×106/kg（1.68×106/kg ～ 8.32× 106/kg）,回输的第三方脐血中CD34＋细胞中位数为1.03×105/kg（0.31×105/kg～5.32×105/kg）.42例（95.45％）患者造血重建,中性粒细胞造血重建时间为14d（10～29 d）,血小板造血重建时间为23d（11～89d）.对42例植入成功的患者长期监测供受体嵌合率（STR）,除5例（11.90％）患者在移植后3～13个月复发,其余37例（88.10％）患者STR均≥95％.17例（40.47％）患者发生不同程度的急性移植物抗宿主病（aGVHD）,发生Ⅱ～Ⅳ度aGVHD的患者共8例（19.05％）,发生Ⅲ～Ⅳ度aGVHD的患者为4例（9.52％）.23例（54.76％）发生慢性移植物抗宿主病（cGVHD）,其中局限型17例（40.47％）,广泛型6例（14.29％）.1年总生存（OS）率为70.84％,1年无事件生存（EFS）率为63.34％.结论 初步研究证实单倍体造血于细胞联合第三方脐血输注治疗白血病安全有效,从而为异基因造血干细胞的移植提供了新的方法.     

T-cell large granular lymphocyte leukemia of donor origin after cord blood transplantation

We report the first case of T-cell large granular lymphocyte leukemia of donor origin after a second cord blood transplantation for acute myeloid leukemia, and review the literature regarding rare cases of T-cell-origin posttransplantation lymphoproliferative disorders.     

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.     

An infant with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation

Here we report a case with precursor natural killer (NK) cell leukemia successfully treated with an unrelated cord blood transplantation. A 7-month-old Japanese boy was diagnosed to have NK cell leukemia based on the existence of abnormal cells in the bone marrow with the phenotype of CD3(-) /CD4(+) /CD7(-) /CD8(-) /CD16(-) /CD33(+) /CD34(-) /CD56(+) /HLA-DR(+) /NKB1(+) / CD94(+). The leukemic cells showed few azurophilic granules in the cytoplasm and weak cytotoxic activity. Although he presented with a huge mass occupying the bilateral paranasal sinuses and hepatosplenomegaly, he achieved complete remission by the conventional chemotherapeutic regimen for acute myelogenous leukemia, followed by an unrelated cord blood transplantation. He has remained in complete remission for 14 months posttransplant. To our knowledge, this is the youngest reported case with precursor NK cell leukemia; cord blood transplantation may thus be the treatment of choice for this disease.     

Successful unrelated cord blood transplantation for relapse after autologous transplantation in non-Hodgkin's lymphoma

We report a 34-year-old male with relapsed non-Hodgkin's lymphoma (NHL) after autologous peripheral blood stem cell transplantation successfully treated with unrelated cord blood transplantation (CBT). The conditioning regimen included 12 Gy total body irradiation and cyclophosphamide. After the conditioning, a total of 3.14 x 10(7)/kg cord blood nucleated cells was infused on 14 February 2000. An absolute neutrophil count greater than 5 x 10(8)/l and a self-sustained platelet count greater than 50 x 10(9)/l were achieved on days 21 and 43, respectively. During the follow up period, grade I acute graft-versus-host disease (GVHD) and limited chronic GVHD occurred, but both were successfully treated with a dose modification of cyclosporine. After a follow-up period of 16 months, the patient is alive and free of disease. To our knowledge this is the first report of a successful unrelated CBT for an adult NHL patient who relapsed after autologous transplantation.     

HTLV-related markers in a Hungarian patient with adult T-cell leukemia.

Monoclonal integration of DNA sequences related to, but not identical to HTLV-I provirus was detected in the peripheral blood lymphocytes of a Hungarian male suffering from ATL. The patient and his parents showed serological cross-reactivity with both HTLV-I and HTLV-II group-specific antigens. Restriction enzyme analysis with EcoRI, PstI, BamHI, HindIII and SacI revealed structural similarity of the provirus integrated in the DNA of ATL cells to HTLV-I but not to HTLV-II. Data suggest that this provirus and HTLV-I are similar to each other along gag and pol regions, but they are different in the env region.     

Production of vascular endothelial growth factor in T-cell prolymphocytic leukemia

We describe a 79-year-old man who had massive pleural effusion and a proliferation of prolymphocytic leukemia cells in the peripheral blood, bone marrow, and pleural effusion fluid. Immunophenotyping of leukemia cells revealed either CD3+CD4+CD8-CD25+ or CD3+CD4+CD8+CD25+. The antibody against human T-cell lymphotropic virus type I was negative. A diagnosis of T-PLL was made. The level of VEGF in the plasma or pleural effusion fluid was very high. Moreover, polymerase chain reaction analysis demonstrated an expression of VEGF mRNA in the leukemia cells, indicating a production of VEGF from leukemia cells and its involvement in the pathogenesis of T-PLL.     

T-细胞幼淋巴细胞白血病治疗的研究进展

幼淋巴细胞白血病（prolymphocytic leukemia,PLL）是一种罕见但恶性程度极高的成熟淋巴肿瘤,其中T-细胞幼淋巴细胞白血病（T-cell prolymphocytic leukemia,T-PLL）这种亚型被认为难以治愈,临床治疗目的主要是提高治疗有效率和延长缓解期。随着对白血病发生发展机制研究的不断深入,目前T-PLL的治疗手段取得了较大的进步,其中表观遗传学的干预治疗为治愈TPLL提供了新的研究方向,本文就T-PLL的治疗研究进展进行综述。      

Jejunal perforation in a patient with adult T-cell leukemia

We present a case of adult T-cell leukemia (ATL) with jejunal perforation at the site of intestinal involvement by ATL. A 39-year-old woman presented with sudden-onset abdominal pain. Physical examination showed generalized severe abdominal tenderness and intraabdominal free air was seen on radiographic examination. Under a diagnosis of peritonitis due to intestinal perforation, an emergency operation was performed. A pinhole-like perforation was found in the jejunum 80 cm distal to Treitz's ligament, and the patient underwent partial resection of the affected jejunum. Microscopic examination revealed diffuse infiltration of abnormal lymphocytes into the entire wall of the jejunum and mesenteric lymph nodes. A diagnosis of ATL was confirmed by the presence of antibody to human T-lymphotropic virus type 1 (HTLV-1) in the serum, a positive result for T-cell markers and the HTLV-1 proviral genome in the mononuclear cells in the specimens. The final diagnosis was thus lymphoma subtype of ATL. Combination chemotherapy was repeated until the patient died 14 months postoperatively. Emergent surgery followed by intense chemotherapy might improve survival in patients with ATL and perforated intestine.     

The efficacy of unrelated cord blood transplantation for adult myelodysplastic syndrome

Although allogeneic stem cell transplantation from a human leukocyte antigen (HLA)-identical related donor offers a potential cure for patients with myelodysplastic syndrome (MDS), a suitably matched related donor is unavailable for approximately two thirds of patients. Recently, umbilical cord blood from unrelated donors have been used as an alternative stem cell source for adult patients with MDS. Here, we updated the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning for 22 adult patients with MDS. Diagnosis at transplantation included refractory anemia (RA) (n = 3), refractory anemia with excess blasts (RAEB) (n = 2), RAEB-t (n = 2), and MDS-related secondary acute myeloid leukemia (AML) (n = 15). All patients were treated with total body irradiation (12 Gy), cytosine arabinoside (Ara-C) and cyclophosphamide followed by unrelated HLA-mismatched CBT. The median age was 40 years (range, 19 - 51 years), the median weight was 54.5 kg (range, 43 - 75 kg), and the median number of cryopreserved nucleated cells was 2.43 × 10⁷/kg (range, 1.82 - 4.10 × 10⁷/kg). Twenty one patients had myeloid reconstitution and the median time to more than 0.5 × 10⁹/l absolute neutrophil count was 22.5 days. A self-sustained platelet count more than 50 × 10⁹/l was achieved in 19 patients at a median time of 49 days. Acute GVHD above grade II occurred in seven of 21 evaluable patients and chronic GVHD in 16 of 19 evaluable patients. Among 16 chronic GVHD patients, in eight patients the disease was extensive. Seventeen patients are alive and free of disease at between 371 and 2562 days after transplantation. With a median follow-up of 1505 days, the probability of disease-free survival at 4 years was 76.0%. These results suggest that adult MDS patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.