Adult T-cell leukaemia/lymphoma (ATLL) is a rare T lymphoproliferative disorder which is aetiologically linked with human T-cell lymphotropic virus type-1 (HTLV-1). HTLV-1 is endemic in Japan, Caribbean and Africa. The highest incidence of ATLL is in Japan although sporadic cases have been reported elsewhere in the world. We describe a case of ATLL with an unusual presentation which we believe is the first reported case of ATLL in Malaysia based on our literature search. A 51-year-old Indian lady was referred to University Malaya Medical Centre for an incidental finding of lymphocytosis while being investigated for pallor and giddiness. Clinical examination revealed bilateral shotty cervical lymph nodes with no hepato-splenomegaly or skin lesions. Laboratory investigations showed absolute lymphocytosis (38 x 10(9)/L) with a mildly increased serum lactate dehydrogenase. The peripheral blood smear showed the presence of predominantly small to medium sized, non-flower lymphocytes. The bone marrow showed similar findings of prominent lymphocytosis. Immunophenotyping of the bone marrow mononuclear cells showed CD3+, CD4+, CD5+, CD7- and CD25+ which is characteristic of ATLL phenotype. HTLV-1 infection was confirmed by the presence of HTLV-1 proviral DNA in the tumor cells using conventional Polymerase Chain Reaction (PCR) and real-time PCR. Here, we discuss the pathogenesis and characteristics of ATLL as well as the detection of HTLV-1 by real time PCR.
Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated ; Human T-lymphotropic virus 1 ; Polymerase Chain Reaction ; T-Lymphocytes ; Lymphocytosis

The clinicopathologic features of a Korean patient with adult T-cell leukemia/lymphoma(ATLL) are presented. A 51-year-old man, who has lived in Korea since birth, had multiple cutaneous nodules and multiple lymphadenopathy for the previous two months. A histopathologic study of the lymph node and skin lesion revealed T-cell non-Hodgkin's lymphoma of pleomorphic type, medium and large cell type. Peripheral blood examination showed leukemic features with 30% of abnormal lymphoid cells. HTLV-I proviral DNA pX region was detected in the DNA from peripheral blood mononuclear cells(PBMC) and the specific gag, pol, and env HTLV-I sequences were detected in the lymph node using polymerase chain reaction technique. Human T-cell leukemia/lymphoma type I(HTLV-I) antibodies were present in the serum. An immunophenotypic study of the lymph node revealed CD4 positive and CD8 negative helper/inducer T cell type surface markers. This case is the acute type, i.e. prototypic ATLL. He was treated with an intensive chemotherapy including cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone. Despite initial transient improvement, the tumor progressed after three cycles of the regimen and became refractory to further chemotherapy. These clinicopathologic findings, including the immunophenotypic analysis, established with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Case Report ; Cyclophosphamide/administration & dosage ; DNA, Viral/blood ; Doxorubicin/administration & dosage ; Etoposide/administration & dosage ; Human ; Human T-lymphotropic virus 1/isolation & purification ; Immunophenotyping ; Korea/epidemiology ; Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/drug therapy/epidemiology/pathology/virology ; Lymph Nodes/pathology ; Male ; Middle Age ; Prednisone/administration & dosage ; Proviruses/isolation & purification ; Tumor Stem Cells/chemistry/pathology ; Vincristine/administration & dosage

Humans ; Adult ; Consensus ; Lymphoma, Non-Hodgkin ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes ; China

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% <i>vsi> 55.6%, <i>Pi>=0.001; 5-year PFS: 8.9% <i>vsi> 54.2%, <i>Pi><0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (<i>Pi>=0.271, <i>Pi>=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% <i>vsi> 0) for the 17 PR cases (<i>Pi>=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% <i>vsi> hap-haploidentical of 63.6% <i>vsi> unrelated donor of 50.0% (<i>Pi>>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 <i>vsi> 12.6%, <i>Pi>=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% <i>vsi> 62.9%, <i>Pi>=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (<i>Pi><0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.
Adult ; Adolescent ; Humans ; Prognosis ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Hematopoietic Stem Cell Transplantation ; Lymphoma, T-Cell ; Unrelated Donors

It is difficult to distinguish between circulating lymphoma cells and non-lymphoma cells which are lymphocytes, activated lymphocytes, monocytes, and leukemic cells. The presence of circulating lymphoma cells in the peripheral blood is infrequent but the incidence is probably significantly higher than has been reported in morphologic studies of peripheral blood smears. So the morphologic evaluations of the circulating lymphoma cells and non-lymphoma cells are needed. We experienced that circulating lymphoma cells were found in the peripheral blood smears in the 4 cases of non-Hodgkin's lymphomas. They were consisted of mantle cell lymphoma (1 case), peripheral T cell lymphoma (1 case), adult T cell leukemia/lymphoma (1 case), cutaneous T cell lymphoma (1 case) and diagnosed from their lymph node biopsies. Those circulating lymphoma cells were morphologically observed by light and electron microscopic methods. Using those morphological features, we think that detection rate of circulating lymphoma cells can be improved in the patient with lymphoma.
Adult ; Biopsy ; Humans ; Incidence ; Leukemia ; Lymph Nodes ; Lymphocytes ; Lymphoma* ; Lymphoma, Mantle-Cell ; Lymphoma, Non-Hodgkin* ; Lymphoma, T-Cell, Cutaneous ; Lymphoma, T-Cell, Peripheral ; Monocytes

Human T-cell lymphotrophic virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). The viral transcriptional activator Tax encoded by the HTLV-I genome is thought to play critical roles in the activation of nuclear factor kappaB(NF-kappaB) as well as in the transformation of human T lymphocytes and the induction of tumor and leukemia. In this report, we suggest that RelA subunit of NF-kappaB might play an important role in Tax-induced p53 inactivation. Using antisense oligonucleotides, the ability of Tax inhibiting p53 transactivation was blocked by RelA, but not p50 or c-rel, antisense oligonucleotides in C81 HTLV-1-transfected cell line. The inability of p50 or c-rel antisense oligonucleotides in blocking the Tax-mediated inhibition of p53 function was not due lack of activity, since NF-kappaB activation was specifically blocked by these oligonucleotides. Also, we demonstrate by using co-immunoprecipitation assays that p53 interacts with RelA in HTLV-I transformed cells and their binding became stronger by the overexpression of Tax in 293T cells. These results suggest the possibility that the physical interaction between p53 and RelA correlates with Tax-induced p53 inhibition.
Cell Line ; Genome ; Human T-lymphotropic virus 1 ; Humans* ; Immunoprecipitation ; Leukemia ; Leukemia-Lymphoma, Adult T-Cell ; NF-kappa B* ; Oligonucleotides ; Oligonucleotides, Antisense ; T-Lymphocytes* ; Taxes ; Transcriptional Activation

OBJECTIVETo evaluate the safety of polyethylene glycol conjugated L-asparaginase (PEG-Asp) for patients with adult acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin lymphoma (T-NHL).

METHODSA retrospective analysis was conducted on the clinical data of 101 young patients (≤40 years old) with ALL and T-NHL, diagnosed at Peking Union Medical College Hospital between January 2012 and June 2014.

RESULTSA total of 480 doses of PEG-Asp were administered in 44 cases with ALL and 57 patients with T-NHL. Only one patient (0.2%) experienced mild allergic reaction. Other grade 3 or 4 toxicities of non-hematologic effects included low level of fibrogen (6.4%), elevated ALT (4.4%), blood glucose (2.3%), and triglyceridemia (2.3%), decreased albumin (0.8%) and elevated amylase (0.2%). Furthermore, 5 cases (1.0%) developed venous thrombosis, 9 cases (1.9%) hemorrage, 1 patient (0.2%) non-necrosis pancretitis.

CONCLUSIONThe risk of allergic reaction incurred by PEG-Asp is very low. It can be used safely in ALL and T-NHL. Coagulation status should be monitored during the treatment.

We experienced a 22-year old patient with a documented history of minimal change nephrotic syndrome (MCNS), and a diagnosis of acute lymphoblastic leukemia (ALL) was then made for this patient. The patient received standard daily steroid therapy for the treatment of nephrotic syndrome. Cyclosporin A was administered because there was no clinical improvement with steroid therapy. Six years after the diagnosis of nephrotic syndrome, the patient was diagnosed with ALL. After chemotherapy for ALL, the patient was in complete remission and he showed clinical improvement of nephrotic syndrome. The hematological malignancies associated with nephrotic syndrome are mainly lymphoma and chronic lymphocytic leukemia. ALL has rarely been described in combination with nephrotic syndrome. Although the exact mechanism for development of ALL after nephrotic syndrome is unknown, at least two possibilities exist. First, the incidence of leukemia may be increased after immunosuppressive therapy, which may include cyclosporin A. Second, the underlying defect in T-lymphocyte function could account for both nephrotic syndrome and ALL. The possible mechanisms for such a relationship are discussed here along with a review of the relevant literature.
Cyclosporine ; Diagnosis ; Drug Therapy ; Hematologic Neoplasms ; Humans ; Incidence ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell ; Lymphoma ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; T-Lymphocytes ; Young Adult

One case of arthritis complicating leukemia is described in which leukemic cells were identified in synovial fluid by light microscopy. Although arthritis is a well-known manifestation of leukemia with an incidence of 13.5%, the pathogenesis often is unclear, and the direct demonstration of leukemic cells in synovial fluid has been very uncommon. A 16 year-old male patient was admitted due to left elbow joint pain and swelling. Synovial fluid examination revealed blast cells and this finding has directed to a final diagnosis of acute lymphoblastic leukemia.
Adolescent ; Arthritis/*etiology ; Humans ; Leukemia-Lymphoma, Adult T-Cell/*complications/diagnosis/pathology ; Male

OBJECTIVETo analyze clinical feature and curative efficacy of patients with T cell lymphoblastic lymphoma(T-LBL).

METHODSThe clinical data including clinical features, laboratorial results, survival and prognostic factors from 30 patients with T-LBL were retrospectively analyzed.

RESULTSMedian age of 30 cases was 24.5 years, 25 (83.3%) patients were at high-intermediate and high risk by IPI, extranodal disease was present in 73.3% of the patients, 17(56.7%) patients had bone marrow involvement and 19(63.3%) had mediastinal masses. The overall response rate(ORR) for the whole group was 80.0%, the complete response rate was 36.7%, the 3-5-year overall survival rate was 37.1% and 26.0%, respectively. Compared with NHL-like regimens, ALL-like chemotherapy could improve the survival of patients, the 3-year overall survival rate was 59.1% vs 27.3%. For adult patients, the median overall survival time was 35 months vs 13 months in HSCT group and chemotherapy group, there was a statistically significant difference(P=0.019). ECOG score, IPI score, anemia, the level of LDH and β2-MG, therapy regimens, the short-term efficacy and the level of fibrinogen were the related factors for prognosis.

CONCLUSIONT-LBL is more common in young men, with large mediastinal mass and bone marrow involvement. ALL-like chemotherapy regimens are superior to NHL-like regimens, HSCT can improve the survival and reduce the recurrence of adult patients. Chemotherapy combined with allogeneic DC/CIK immune cell treatment can be used in relapsed patients.