Recurrent Anaplastic Large Cell Lymphoma Research Articles

Long‐term survival of a child with refractory anaplastic large cell lymphoma following therapy with an antisense oligonucleotide, topotecan, and vinblastine

Anaplastic large cell lymphoma includes a subset of highly aggressive tumours and has a relapse rate of 30% at 2 years. Relapsed patients often have poor clinical outcome. The use of antisense oligonucleotides to down-regulate Bcl-2 protein can reverse chemotherapy resistance. The authors describe an 11-year-old boy with recurrent anaplastic large cell lymphoma who had received double high-dose chemotherapy followed by autologous haematopoietic stem-cell transplantation, had refractory disease and then had achieved long-term remission with the use of an antisense oligonucleotides in combination with vinblastine and topotecan.

Adult anaplastic large cell lymphoma involving the central nervous system: a rare clinical scenario

Dear Editor, Anaplastic large cell lymphoma (ALCL) is a rare T-cell non-Hodgkin lymphoma with distinct pathologic features characterized by CD30 expressing large pleomorphic lymphoid cells with or without anaplastic lymphoma kinase (ALK) gene rearrangement. The disease commonly spreads to bone marrow, skin, lung, liver, and, rarely, other sites [1]. ALCL rarely occurs in the central nervous system (CNS), of which most are primary ALCL reported in pediatric or immunocompromised patients [2]. ALCL with secondary CNS involvement is extremely rare [3]. Here, we present two adult patients having ALCL with secondary CNS involvement, both treated with standard chemotherapy and autologous hematopoietic stem cell transplant (auto-SCT), and both patients had a relatively long survival. To date, only three other similar cases have been reported and all had much shorter survival with no auto-SCT treatment. A 27-year-old man who presented with a mediastinal mass and general lymphoadenopathy was subsequently diagnosed with ALK-positive ALCL. The tumor cells expressed CD30 and ALK. He received cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone (CHOP) chemotherapy along with prophylactic high-dose intrathecal methotrexate for three cycles. One year after the initial diagnosis of ALCL, the patient developed seizures. Contrast-enhanced brain MRI revealed diffuse edema in both the parietal and occipital regions. There was also evidence of parenchymal disease both above and below the tentorium in addition to diffuse pial enhancement and dural involvement (Fig. 1a and b). Cerebrospinal fluid (CSF) cytospin examination revealed a population of large anaplastic lymphoid cells in the background of few granulocytes and macrophages. Flow cytometry of the CSF identified abnormal T cells expressing CD30 and CD4 with loss of other pan-T-cell markers (CD3, CD5, and CD7). A T-cell gene rearrangement analysis of the CSF DNA sample detected a prominent but dim T-cell receptor gamma monoclonal peak. No circulating lymphoma cells were identified in the peripheral blood at that time point. The patient received intrathecal methotrexate and cytarabine followed by wholebrain radiation. His disease was well controlled although it was complicated with severe encephalopathy and cerebral infarct, which caused peripheral vision loss. Five years later, he developed severe abdominal pain and diarrhea. PET/CT scan revealed hypermetabolic activity in the distal duodenum, and biopsy was consistent with recurrent ALCL X. Zhang Department of Pathology and Cell Biology, University of South Florida College of Medicine, Tampa, FL, USA

Allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning for a child with recurrent anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence is frequently observed. Allogeneic hematopoietic stem cell transplantation (HSCT) has recently been reported to be effective against recurrent disease, suggesting a graft-versus-lymphoma effect. We present a 3-year-old child with recurrent ALCL who underwent HSCT from an HLA-1-locus mismatched cord blood unit following reduced intensity conditioning with fludarabine, melphalan, and low-dose thoraco-abdominal irradiation. Engraftment was uneventful, but grade III acute graft-versus-host disease was observed. He is well and free of disease 25 months after HSCT, which implies that reduced intensity conditioning may allow a sufficient graft-versus-lymphoma effect against ALCL while lessening treatment-related toxicities.

Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use

The successful resumption of high-dose methotrexate in a 13-year-old boy with recurrent anaplastic large-cell lymphoma (ALCL) who suffered renal dysfunction after a 24-hour infusion of high-dose methotrexate and required treatment with carboxypeptidase G(2) (CPDG(2) ) is described. A 13-year-old boy who had been diagnosed in 2001 with stage I ALCL was admitted to the hospital in February 2005 after he developed a smaller left axillary mass in the area of his original mass. Recurrent ALCL was diagnosed, and treatments were initiated based on branch K3 of the protocol published in the non-Hodgkin's lymphoma-Berlin-Frankfurt-Münster (NHL-BFM) trial 90. In the NHL-BFM 90 protocol, all AA and BB courses include high-dose methotrexate therapy, which consists of aggressive alkalinized hydration, methotrexate 5 g/m(2) given as an i.v. infusion over 24 hours, and leucovorin rescue. During course BB2, the boy's serum methotrexate values exceeded NHL-BFM goals at 36, 42, and 48 hours. Because the patient's elimination of methotrexate remained slow and his serum creatinine level remained above normal limits, CPDG(2) was obtained for the treatment of methotrexate toxicity. The patient tolerated the CPDG(2) without adverse effects, and the patient's serum methotrexate concentration decreased from 14.47 to 0.66 microM. The patient went on to complete six courses based on the protocol. High-dose methotrexate was resumed at 50% then 100% of the original dose. He is currently in remission on maintenance therapy. A 13-year-old boy with recurrent ALCL had methotrexate-induced nephrotoxicity following high-dose methotrexate. The resultant delayed methotrexate clearance required the standard therapies as well as use of investigational CPDG(2). High-dose methotrexate was successfully resumed.

Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan

This report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10.5 months after the initial diagnosis. Twenty-four patients achieved a second remission. After a median follow-up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse-free survival rates were 61 +/- 12% and 51 +/- 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.

“Wreath cell” in recurrent anaplastic large cell lymphoma

“Wreath cell” in recurrent anaplastic large cell lymphoma

Characterization of a Novel Human Anaplastic Large Cell Lymphoma Cell Line Tumorigenic in SCID Mice

L82, a novel anaplastic large cell lymphoma (ALCL) cell line was established from the pleural effusion of a 24-year-old patient with recurrent ALCL. L82 cells showed the typical morphologic features of ALCL cells with irregular, often indented, nuclear profiles, prominent nucleoli, and abundant cytoplasm. The immunoprofile of L82 corresponds to that seen typically in primary ALCL cells, with positivity for CD30, EMA, CD3, CD4, CD25, CD71, TIA1, and granzyme B; the cells were negative for EBV-related antigens. Cytogenetic analysis showed a complex, near triploid karyotype with 72-77 chromosomes, including the ALCL specific translocation t(2;5)(p23;q35). Chromosomal analysis revealed a number of secondary structural alterations including amplification of 7q21-31, 1q, and 6p, and gain of chromosomal material in 8q (affecting the c-myc gene). The rearrangement of the T-cell receptor- γ locus shows that L82 is clonally derived from T-lineage lymphoid cells. mRNAs for interleukin 7(IL-7), IL-8, IL-9, IL-10, TNF- β, and for the IL-7 and IL-9 receptor were found. These data show that the T-helper cell (Th)1/Th2 balance was polarized to Th2. L82 were inoculated intraperitoneally into 4 week-old SCID mice and produced a disseminated tumor within 4-6 weeks. Morphological, immunohistochemical, and molecular genetic investigation confirmed that the xenograft and the original ALCL tumor were identical. SCID mice xenografted with the human ALCL cell line, L82, provide a useful model system for the investigation of the biology of ALCL and of new therapeutic approaches, such as specific immunotherapy.