Primary Cauda Equina T-Cell Lymphoblastic Lymphoma.

BACKGROUND: T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive form of non-Hodgkin lymphoma. This report describes, to our knowledge, the first adult case of a primary cauda equina T-LBL. Treatment consists of multiagent chemotherapy, and surgical removal of T-LBL does not improve outcome. We discuss the workup of patients with an intradural spinal mass, together with a review of the literature on primary spinal lymphoma of the cauda equina. CASE DESCRIPTION: A 54-year-old woman with Crohn's disease, for which she was taking immunosuppressive medication, presented with progressive back pain radiating to both legs and deteriorating neurologic deficits caused by an intradural, contrast-enhancing lesion in the L1-5 region. During acute surgery, the tumor was partially resected. Immunohistochemical phenotyping revealed a T-LBL. No other lymphoma localizations were found after subsequent staging. Despite extensive treatment, the patient died of disseminated disease throughout the central nervous system, 6 weeks after the diagnosis. CONCLUSIONS: Pain and progressive neurologic complaints can be symptoms of a (malignant) intradural spinal tumor. Intradural lymphoma must be considered as a differential diagnosis by clinicians because it can mimic neoplasms that often require urgent surgery. The histopathologic diagnosis should preferably be obtained by way of cerebrospinal fluid analysis or tumor biopsy because tumor resection has no beneficial effect on the oncologic outcome.

Parotitis due to Burkholderia cepacia infection after autologous hematopoietic stem cell transplantation.

Burkholderia cepacia predominantly causes opportunistic infections in hospitalized and immunocompromised patients such as patients with cystic fibrosis, cancer, or human immunodeficiency virus (HIV). Nonetheless, Burkholderia cepacia is infrequently reported to cause infection in hematopoietic stem cell transplantation (HSCT) recipients. Herein, we report a rare case of suppurative parotitis in a 31-year-old patient with T-cell lymphoblastic lymphoma (T-LBL) who underwent auto-HSCT. The secretion from the Stensen duct was collected, and Burkholderia cepacia was detected using the VITEK-2 identification system. Additionally, sensitive antibiotic therapy against this bacterium was also effective. This is the first case of parotitis triggered by Burkholderia cepacia after auto-HSCT, and it is also the first reported domestic case. This case emphasizes the importance of considering bacterial infections in general and Burkholderia cepacia specifically in HSCT patients with post-transplant parotitis.

Cytomegalovirus pneumonia in a patient with T-lymphoblastic leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: A case report.

RATIONALE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for hematological malignancies. Common complications are opportunistic infections and graft-versus-host disease (GVHD). Cytomegalovirus (CMV) is one of the most common causes of opportunistic infections. PATIENT CONCERNS: A 30-year-old male was diagnosed with T-cell lymphoma after persistent cough and lymphadenopathy. Fever, abdominal pain, diarrhea, rash, and dyspnea occurred after HSCT. DIAGNOSIS: The young man developed severe CMV infection with CMV detected in the bronchoalveolar lavage fluid and gastrointestinal tract. INTERVENTIONS: Intravenous ganciclovir and high-dose glucocorticoids were administered after the patient was diagnosed with CMV pneumonia and enteritis. OUTCOMES: After 3 weeks, the young man died from respiratory failure and infectious toxic shock caused by severe CMV infection. LESSONS: Patients after HSCT should be closely monitored CMV-DNA in blood and other specimen, and treated first if necessary, so as to avoid the occurrence of severe infections such as CMV gastroenteritis and pneumonia.

T-cell lymphoblastic lymphoma involving the ocular adnexa: report of two cases and review of the current literature.

The majority of ocular adnexal lymphomas are B-cell in origin. We report two cases of T-cell lymphoblastic lymphoma (T-LBL) involving the ocular adnexa. One patient presented with a painless pink conjunctival lesion and inferior orbital fullness. The second patient presented with a painless orbital mass. The diagnoses were confirmed by histopathology and immunohistochemistry. Both patients had extensive multifocal lesions during staging. Prompt intensified chemotherapy regimens were initiated. T-LBL is an aggressive disease with poor prognosis. This report emphasizes the importance of timely diagnosis by the ophthalmologist with co-management and treatment with an oncologist.

Primary T-cell lymphoblastic lymphoma in the middle ear.

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

[Autologous hematopoietic stem cell transplantation as late high-dose consolidation in adult patients with T-cell lymphoblastic leukemias: Results of a Russian multicenter study].

AIM: To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01 193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy. SUBJECTS AND METHODS: Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group. RESULTS: The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a.higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047). CONCLUSION: The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.

Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass.

We report a case of a 62-year-old man with concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Computed tomography revealed a 5.5-cm anterior mediastinal mass, and surgical resection was performed. Histologically, the mass showed concurrent thymoma (type AB), thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Lymphoma cells infiltrated in the left lung, pulmonary hilar lymph nodes, and involved bone marrow. The patient underwent chemotherapy for T lymphoblastic leukemia/lymphoma and achieved remission. One year after surgery, he remains free of both thymoma and thymic carcinoma, and T lymphoblastic leukemia/lymphoma remains complete remission under maintenance therapy. Thymoma and T lymphoblastic leukemia/lymphoma can combine in the same mass, although this is quite rare. At the time of the diagnosis of thymoma, additional attention should be directed toward lymphocytes in the background.

Indolent T-lymphblastic proliferation: report of a case involving the upper aerodigestive tract.

T-lymphoblastic lymphoma (T-LBP) is a high-grade malignant lymphoma, which possesses the characteristic of high metastasis and high mortality without treatment. We are presenting a special T-lymphoblastic proliferation involving in the oropharynx, nasopharynx, sinus and trachea in a patient with local involved about 15-years without systemic dissemination. The immunophenotype of this case was similar to T-LBP. The proliferous cells were positive for terminal deoxynucleotidyl transferase (TdT), CD3, and appeared co-expression CD4 and CD8. No clonal rearrangements of TCRγ and/or TCRß gene were detected. Indolent T-lymphoblastic proliferations rarely occurred or unusually could not be diagnosed, combing with the relevant literature and clinically indolent manifestation, we interpreted this case as indolent T-lymphoblastic proliferation (iT-LBPs). So far, the mechanism of the T-lymphoblastic proliferations is still uncertain and requires further study.

A 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia.

Chronic kidney disease is common in pediatric patients following hematopoietic stem cell transplant. Its etiology is likely multifactorial and depends both on pre-conditioning regimens as well as immunosuppressive therapy and posttransplant prophylactic medications. Graft vs. host disease (GVHD) is a common sequela of hematopoietic stem cell transplant and has been associated with the nephrotic syndrome (NS). Here we report a case of a pediatric patient who developed proteinuria and renal insufficiency after stem cell transplant. A kidney biopsy showed chronic interstitial nephritis and extensive foot process effacement, which are likely sequelae of GVHD. Moreover we show decreased CD4 and CD3 lymphocyte counts in the interstitial infiltrate, suggesting that abnormal lymphocyte response might play a role in podocyte injury following GVHD. This case illustrates the importance of the kidney biopsy in the assessment of stem cell transplant-mediated renal failure.

Notch1 gene mutations target KRAS G12D-expressing CD8+ cells and contribute to their leukemogenic transformation.

Acute T-cell lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive hematopoietic malignancy affecting both children and adults. Previous studies of T-ALL mouse models induced by different genetic mutations have provided highly diverse results on the issues of T-cell leukemia/lymphoma-initiating cells (T-LICs) and potential mechanisms contributing to T-LIC transformation. Here, we show that oncogenic Kras (Kras G12D) expressed from its endogenous locus is a potent inducer of T-ALL even in a less sensitized BALB/c background. Notch1 mutations, including exon 34 mutations and recently characterized type 1 and 2 deletions, are detected in 100% of Kras G12D-induced T-ALL tumors. Although these mutations are not detected at the pre-leukemia stage, incremental up-regulation of NOTCH1 surface expression is observed at the pre-leukemia and leukemia stages. As secondary genetic hits in the Kras G12D model, Notch1 mutations target CD8(+) T-cells but not hematopoietic stem cells to further promote T-ALL progression. Pre-leukemia T-cells without detectable Notch1 mutations do not induce T-ALL in secondary recipient mice compared with T-ALL tumor cells with Notch1 mutations. We found huge variations in T-LIC frequency and immunophenotypes of cells enriched for T-LICs. Unlike Pten deficiency-induced T-ALL, oncogenic Kras-initiated T-ALL is not associated with up-regulation of the Wnt/ß-catenin pathway. Our results suggest that up-regulation of NOTCH1 signaling, through either overexpression of surface NOTCH1 or acquired gain-of-function mutations, is involved in both T-ALL initiation and progression. Notch1 mutations and Kras G12D contribute cooperatively to leukemogenic transformation of normal T-cells.

Allogeneic hematopoietic stem cell transplantation in adolescent and adult patients with high-risk T cell acute lymphoblastic leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (≥CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR T-ALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in ≥CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in ≥CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P = .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in ≥CR2. On multivariate analysis, disease status at SCT remained significantly associated with OS (P = .007), DFS (P = .002), and CIR (P = .000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P = .006) and DFS (P = .01). Our data indicate that allo-SCT represents an effective treatment for HR T-ALL, particularly when performed in CR1.

Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15.

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL.

Unmanipulated haploidentical peripheral blood stem cell transplantation for precursor T-cell lymphoblastic lymphoma relapsed after autologous PBSCT.

Precursor T-cell lymphoblastic lymphoma (T-LBL) is a clinically aggressive disease, associated with a high subsequent relapse rate. We treated a pediatric patient with T-LBL who relapsed after an autologous peripheral blood stem cell transplantation. Unmanipulated peripheral blood was used as a source for the graft. Hematopoietic engraftment was prompt and the risk of graft-versus-host disease was acceptable. The patient has been in continuous complete remission without chronic graft-versus-host disease for 32 months. Hence, haploidentical peripheral blood stem cell transplantation might be one of the adoptive options for salvage therapy in patients with recurrent or refractory T-LBL, and unmanipulated peripheral blood might be acceptable as a graft.

The monitoring of hematopoietic stem cell transplant donors and recipients from endemic areas for malaria.

Malaria is an unusual complication after hematopoietic stem cell transplantation in non-endemic countries. However, transplant candidates, recipients and donors living in endemic regions frequently report previous episodes of malaria. This fact could represent an important risk for immunosuppressed recipients that could develop severe malaria cases. We report a case of hematopoietic stem cell transplant (HSCT) in which the donor had a history of previous malaria, and close monitoring was performed before and after procedure by parasitological and molecular tests. The donor presented Plasmodium vivax in thick blood smears one month after transplant and was treated according to Brazilian Health Ministry guidelines. The polymerase chain reaction (PCR) was able to detect malaria infection in the donor one week earlier than thick blood film. Even without positive results, the recipient was pre-emptively treated with chloroquine in order to prevent the disease. We highlight the importance of monitoring recipients and donors in transplant procedures with the aim of reducing the risk of malaria transmission.

The monitoring of hematopoietic stem cell transplant donors and recipients from endemic areas for malaria / Monitoramento de doadores e receptores provenientes de áreas endêmicas para malária em transplante de células-tronco hematopoiéticas

Malaria is an unusual complication after hematopoietic stem cell transplantation in non-endemic countries. However, transplant candidates, recipients and donors living in endemic regions frequently report previous episodes of malaria. This fact could represent an important risk for immunosuppressed recipients that could develop severe malaria cases. We report a case of hematopoietic stem cell transplant (HSCT) in which the donor had a history of previous malaria, and close monitoring was performed before and after procedure by parasitological and molecular tests. The donor presented Plasmodium vivax in thick blood smears one month after transplant and was treated according to Brazilian Health Ministry guidelines. The polymerase chain reaction (PCR) was able to detect malaria infection in the donor one week earlier than thick blood film. Even without positive results, the recipient was pre-emptively treated with chloroquine in order to prevent the disease. We highlight the importance of monitoring recipients and donors in transplant procedures with the aim of reducing the risk of malaria transmission.

A malária é complicação incomum após o transplante de células-tronco hematopoiéticas em países endêmicos. No entanto, candidatos a transplantes, receptores e doadores que vivem em regiões endêmicas frequentemente relatam episódios anteriores de malária. Este fato pode representar um risco importante para receptores imunossuprimidos, que podem desenvolver casos de malária grave. Relatamos um caso de transplante de células-tronco hematopoiéticas (TCTH) em que o doador teve história de malária anterior e um monitoramento por meio de exames parasitológicos e moleculares foi realizado antes e após o procedimento. O doador apresentou Plasmodium vivax na gota espessa um mês após o transplante e foi tratado de acordo com as orientações do Ministério da Saúde brasileiro. A reação em cadeia da polimerase (PCR) foi capaz de detectar a infecção por malária no doador uma semana mais cedo do que a gota espessa. Mesmo sem resultados positivos, o receptor foi preventivamente tratado com cloroquina, a fim de prevenir as formas sanguíneas assexuadas. Destacamos a importância do monitoramento de receptores e doadores em procedimentos de transplante, com o objetivo de reduzir o risco de transmissão da malária.

[Systemic lymphoma cells with T precursor condition of extreme female genital tract. A case report and literature review]. / Linfoma linfoblástico sistémico de células precursoras T con afección extrema del aparato genital femenino. Reporte de un caso y revisión de la bibliografía.

Primary female genital tract non Hodgkin's lymphoma is a rare presentation for a common disease in the childhood, and its classification as primary extranodal lymphoma is still controversial. There are a few cases reported as a primary precursor B-cell lymphoblastic lymphoma of the female genital tract, but there is not any case reported as primary precursor T-cell lymphoblastic lymphoma of the ovary in childhood. Herein we describe a 16 years old young woman with bilateral ovarian tumors, paraaortic lymphoadenophaty and disseminate disease to the female genital tract including extension of the tumor to neighboring organs like the omentum and the appendix. Exploratory laparatomy were performed with bilateral salpingo-oophorectomy, hysterectomy, omentectomy, appendectomy, pelvic and para-aortic lymphadenectomy, pelvic washings and with biopsy of vaginal vault. The chemotherapy regimen comprised of CHOP (Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone/Prednisolone) and methotrexate, 3 months later presents left facial hemiparesia follow by right facial hemiparesia, 7 months later presents more Central Nervous System (CNS) complications and apparently was complicated with acute lymphocitic leukemia and after 16 months from the diagnosis, following by a torpid evolution, the pacient finally died.

The use of higher dose clofarabine in adults with relapsed acute lymphoblastic leukemia.

The standard dose of clofarabine is 52 mg/m2 for pediatrics and 40 mg/m2 in adults. Clofarabine dosed at 52 mg/m2 was used in adult patients with refractory ALL to maximize response before allo-HSCT. All patients had a significant response to therapy. Published pharmacokinetic analysis revealed no difference in peak plasma or intracellular concentrations at clofarabine dosed above 40 mg/m2, yet inhibition of replication in leukemia cells was only sustained over 24 hr at 55 mg/m2. Despite this, there have been no reports of high dose clofarabine used in this setting. Our experience implies that there may be a niche role for clofarabine in reducing disease burden before allo-HSCT for adults with relapsed ALL.