Spontaneous improvement in a pediatric patient with peripheral T‐cell lymphoma

Peripheral T‐cell lymphoma (PTCL) is rare in children, and it has a poor prognosis compared with other types of lymphoma. We report the case of a 7‐year‐old boy with spontaneous improvement of PTCL complicated by hemophagocytic syndrome as the initial symptom. He complained of pain and swelling of the right neck and presented with high fever. Pancytopenia, liver dysfunction, elevated ferritin and soluble interleukin 2 receptor were noted on laboratory tests. Peripheral blood plasma and white blood cells were positive for Epstein–Barr virus (EBV) genome but, after several days, the fever abated and laboratory data improved. On histopathology of lymph node biopsy, he was diagnosed as having PTCL not otherwise specified (PTCL‐NOS) with EBV infection. He received no chemotherapy and was disease free at the last follow up, 6 years 8 months after onset. This is probably the first case of spontaneous improvement in PTCL‐NOS. Careful treatment planning is therefore necessary in PTCL‐NOS, given the possibility of spontaneous improvement of symptoms.     

Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch‐and‐wait strategy after complete resection

Data on management of pediatric marginal zone lymphoma (MZL) are scarce. This retrospective study assessed characteristics and outcome in 66 patients who were <18 years old. Forty‐four (67%) had an extranodal MZL (EMZL), 21 (32%) a nodal MZL (NMZL), and one patient a splenic MZL. Thirty‐three patients (50%) received a variable combination of adjuvant chemotherapy/immunotherapy/radiotherapy, while the remainder, including 20 of 21 with NMZL, entered an active observation period. Overall survival was excellent (98 ± 2%), although 11 patients relapsed (17%; NMZL, n = 1; EMZL, n = 10), seven after any therapy and four after complete resection only. In conclusion, outcome of NZML, in particular, seems to be excellent after (in)complete resection and observation only.     

TIM‐3 deficiency presenting with two clonally unrelated episodes of mesenteric and subcutaneous panniculitis‐like T‐cell lymphoma and hemophagocytic lymphohistiocytosis

This report offers novel clinical and diagnostic aspects of the association between germline mutations in HAVCR2 and subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL). The patient presented with panniculitis‐like T‐cell lymphoma involving mesenteric fatty tissue associated with hemophagocytic lymphohistiocytosis (HLH). Five years later, he developed a clonally unrelated SPTCL and underwent hematopoietic stem cell transplantation. Retrospectively, he was found to carry germline mutations in HAVCR2 associated with reduced T‐cell immunoglobulin mucin‐3 (TIM‐3) expression. We show that mesenteric fatty tissue localization of SPTCL can be the presenting manifestation of TIM‐3 deficiency, that this condition predisposes to recurrent lymphoma, and that flow cytometry is a possible screening tool.     

Successful treatment of relapsed anaplastic large cell lymphoma with vinblastine monotherapy and allo‐HSCT with reduced intensity conditioning regimen

Relapsed anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence is common. Although vinblastine (VLB) monotherapy is an effective treatment for relapsed ALCL, the optimal treatment duration is unknown, and some patients experience further relapse after completing the treatment. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is also an effective treatment for relapsed ALCL, although transplant‐related toxicity is a problem. Here, we report an 11‐year‐old patient with relapsed ALCL who underwent induction therapy with VLB monotherapy and achieved complete remission (CR) after 12 courses. CR was confirmed on positron emission tomography–computed tomography. The patient then underwent allo‐HSCT with reduced intensity conditioning (fludarabine, melphalan, and low‐dose total body irradiation). He developed grade II acute graft‐versus‐host disease (GVHD), which was successfully treated with methylprednisolone. There was no evidence of chronic GVHD. He has remained in CR without any complications for 19 months after allo‐HSCT.     

CD56‐negative extranodal nasal type NK/T‐cell lymphoma

Extranodal natural killer (NK)/T‐cell lymphoma, nasal type, is a rare lymphoma that occurs predominantly in Asian adults. In this report, we describe the clinical and pathologic features of an unusual aggressive lymphoid neoplasm in a child and review the literature on NK/T‐cell lymphoma in children. The patient was a 4‐year‐old Native American male with facial swelling, lymphadenopathy, and fevers. Biopsy demonstrated neoplastic lymphoid cells that expressed CD3, CD8, TIA‐1, and EBV‐encoded RNA without CD56. The patient failed multiagent chemotherapy and died of therapy‐related complications. This case represents an extranodal NK/T‐cell lymphoma, nasal type, with an unusual lack of CD56. Pediatr Blood Cancer 2010;55:186–189. © 2010 Wiley‐Liss, Inc.     

Sustained first remission in an adolescent with hepatosplenic T‐cell lymphoma treated with T‐cell leukemia induction,nucleoside analog‐based consolidation,and early hematopoietic stem cell transplant

Hepatosplenic T‐cell lymphoma (HTCL) is a rare malignancy. Prognosis is poor with only a few case reports of long‐term survivors. While HTCL universally involves the bone marrow, the condition has been most often treated with multimodal lymphoma specific chemotherapy. We report a durable, sustained first remission in an adolescent treated for HTCL who received induction therapy according to a high risk T‐cell leukemia regimen, a nucleoside analog‐based consolidation, and allogeneic transplantation associated with GVHD. Pediatr Blood Cancer 2009;53:1127–1129. © 2009 Wiley‐Liss, Inc.     

CNS progression during vinblastine or targeted therapies for high‐risk relapsed ALK‐positive anaplastic large cell lymphoma: A case series

Vinblastine and targeted therapies induce remissions in patients with relapsed or progressive anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALCL). Central nervous system (CNS) prophylaxis often is not included during re‐induction in CNS‐negative relapse patients. We report on five patients with progressive or early relapsed ALK‐positive ALCL who developed CNS progression during re‐induction with vinblastine, crizotinib, or brentuximab vedotin given for bridging to allogeneic blood stem cell transplantation. These observations suggest that CNS prophylaxis should be considered in ALCL patients suffering progression during initial therapy who receive re‐induction using agents with limited CNS penetration.     

Results of AIEOP LNH-97 protocol for the treatment of anaplastic large cell lymphoma of childhood

Background

Anaplastic large cell lymphoma (ALCL) represents approximately 15% of all pediatric non‐Hodgkin lymphomas (NHL). It has distinct clinical features, including frequent involvement of extranodal sites and rare localization to the central nervous system (CNS). Despite varying treatment approaches the outcome of patients with ALCL has not significantly improved during the last two decades.

Procedure

From October 1997 to beginning of 2000, newly diagnosed ALCL patients were enrolled into AIEOP LNH‐97 protocol for ALCL. Thereafter and until 2007, only CNS positive patients were included. AIEOP LNH‐97 was based on the BFM‐95 schema for ALCL and included six high‐dose chemotherapy courses. CNS prophylaxis was obtained with one intrathecal injection of chemotherapy in each course, whereas treatment of CNS involvement included three intrathecal injections without irradiation.

Results

Thirty‐two patients were eligible for the study. Lymph‐node disease was the most frequent localization (69% of the cases), followed by mediastinal (25%), CNS (22%), bone marrow (16%), and skin (13%) involvement. Probabilities of overall survival (OS) and of event‐free survival (EFS) at 5 years for the whole population were 87% (SE 6%) and 68% (SE 8%), respectively.

Conclusions

This study confirmed that short pulse chemotherapy is an efficacious treatment option for first line therapy of pediatric ALCL, and that dose intensity may have some relevance for outcome, but not in all of the patients. Refinement and optimization of therapy strategies for ALCL may originate from a combination of clinical and biological prospective studies, as those in the pipeline of current international collaboration. Pediatr Blood Cancer 2012; 59: 828–833. © 2012 Wiley Periodicals, Inc.     

Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T‐cell lymphoblastic lymphoma stage III,detected by flow cytometry (FC) and real‐time quantitative polymerase chain reaction (RQ‐PCR)

Background

Despite overlapping features of T‐cell lymphoblastic lymphoma (T‐LLy) and T‐cell acute lymphoblastic leukemia (T‐ALL), which respond favorably to T‐ALL treatment, clinical and biological differences exist. We retrospectively assessed the prevalence of submicroscopic bone marrow (BM) minimal disseminated disease (MDD) at diagnosis and the early response to treatment (minimal residual disease—MRD) and their prognostic significance in 17 children with stage III T‐LLy treated according to Berlin‐Frankfurt‐Munster (BFM) non‐Hodgkin lymphoma protocols.

Procedure

Four‐color flow cytometry (FC) was used for lymphoma associated immunophenotype and real‐time quantitative polymerase chain reaction (RQ‐PCR) for T‐cell receptor (TCR β/δ/γ) gene rearrangements with at least 0.01% sensitivity.

Results

Two markers per patient were identified in all cases using FC and in 80% using RQ‐PCR. BM MDD at diagnosis of ≥0.01% was detected by FC and RQ‐PCR in 88% and 80% of patients, respectively, and by at least one of the methods in all patients. A significant correlation was achieved between the methods by Pearson correlation analysis (P = 0.004). MRD levels significantly decreased to very low levels on day 33 in 9 out of 10 patients studied. The only patient that remained positive relapsed.

Conclusions

MDD was prevalent in stage III T‐LLy, for which we could not prove a prognostic significance in the context of ALL‐like treatment. This study shows that both FC and RQ‐PCR methods are efficient for MDD and MRD analyses in T‐LLy. Pediatr Blood Cancer 2009;52:20–25. © 2008 Wiley‐Liss, Inc.     

Treatment of pediatric lymphoma in Japan: Current status and plans for the future

Results of pediatric lymphoma treatment have improved markedly over the past 30 years. In Hodgkin's lymphoma, the 5 year event‐free survival (EFS) was 81.5% in a retrospective study. In the ALB‐NHL03 study, the 5 year EFS according to clinical stage in patients with lymphoblastic T‐cell lymphoma (T‐LBL) was 70.6% for stage III and 88.9% for stage IV. In mature B‐cell lymphoma, the B‐NHL03 study indicated that the 4 year EFS according to treatment group was 94% for group 1, 98% for group 2, 84% for group 3, and 78% for group 4. Moreover, the 2 year EFS rate was 81% in Japanese advanced stage patients based on the international ALCL99 study. Thus, EFS >80% was achieved in any subtype of pediatric lymphoma. With regard to refractory or recurrent lymphoma, however, treatment methods for improvement of the survival rate in these patients still need to be developed. Also the difference between child, and adolescent and young adult patients still needs to be clarified, and treatment protocols developed. Although lymphoma treatment does not greatly change according to country, it does differ between other countries and Japan for some subtypes of lymphoma. In particular, the results of treatment of stage III T‐LBL in Japan are worse than those in the USA and Europe. The priority in future studies will be to collect data on these differences, and the reasons for these differences.     

IFR4/MUM1‐positive lymphoma in Waldeyer ring with co‐expression of CD5 and CD10

IRF4/MUM1‐positive lymphoma is a new subgroup of germinal center‐derived B‐cell lymphoma, predominantly involving the Waldeyer ring (WR) in children. CD5 expression is rare in these lymphomas. We report a 7‐year‐old Chinese male with B‐cell lymphoma. Evaluation of his specimen by morphology, immunohistochemistry, and FISH analysis demonstrated IRF4/MUM1‐positive lymphoma with strong and extensive CD5 and CD10 positivity. Despite the lack of t(14;18)(q32;q21) rearrangement, BCL2 protein was expressed. Our report highlights the clinicopathologic features of IFR4/MUM1‐positive lymphoma in WR with co‐expression of CD5 and CD10, and thereby provides insight into this newly recognized disease entity.     

Non‐Hodgkin lymphoma following temozolomide

Temozolomide (TMZ) is an oral alkylating agent with significant activity against glioblastoma multiforme (GBM) and melanoma. It increases survival by 2.5 months when used in combination with radiotherapy as an adjuvant therapy in GBM. Secondary MDS/AML or non‐Hodgkin lymphoma attributed to TMZ exposure has been reported. We report a case of non‐Hodgkin lymphoma secondary to temozolomide in a 20‐year‐old female who was treated for GBM with concurrent TMZ and radiotherapy. She developed lymphoma 2 months after completing chemoradiotherapy. Although she was treated with combination chemotherapy for lymphoma, she died of progressive GBM. Pediatr Blood Cancer 2009;53:661–662. © 2009 Wiley‐Liss, Inc.     

Retinal hemorrhages as a presenting sign in an adolescent patient with hepatosplenic gamma–delta T‐cell lymphoma

Hepatosplenic gamma–delta T‐cell lymphoma is a very rare, aggressive form of peripheral lymphoma first recognized in 1990. Patients often present with organomegaly, anemia, adenopathy, and B symptoms. Rarely in the literature is a pediatric patient described with this subtype of peripheral T‐cell lymphoma. Also, retinal hemorrhages have never been described as a presenting symptom of hepatosplenic gamma–delta T‐cell lymphoma. We describe an adolescent patient with hepatosplenic gamma–delta T‐cell lymphoma who presented with retinal hemorrhages, massive splenomegaly, bone marrow involvement, and B symptoms. Pediatr Blood Cancer 2010;55:190–192. © 2010 Wiley‐Liss, Inc.     

Ongoing remission after intensive All‐type chemotherapy in pediatric intestinal T‐cell lymphoma

A rare case of primary intestinal T‐cell lymphoma (ITL) of an 8‐year‐old boy is reported. Medium‐ to large‐sized tumor cells were βF1+, CD3+, CD8+. TIA‐1+, but CD4?, CD5?, CD30?, CD56?, CD20?, CD79a?, TdT?, consistent with an intraepithelial lymphocyte (IEL) origin. They showed monoclonal rearrangement of the T‐cell receptor γ‐chain and no evidence of EBV infection. No clinical, histologic, laboratory, or genetic evidence of celiac disease was detected. In adults, ITL is often associated with enteropathy and has a very poor outcome. Our patient remains in first remission 30 months after finishing the acute lymphoblastic leukemia protocol COALL‐07‐03 high risk standard. Pediatr Blood Cancer 2010;54:610–612. © 2009 Wiley‐Liss, Inc.     

Lymphoproliferative disorder that resembles heptosplenic lymphoma during maintenance treatment for T‐cell acute lymphoblastic leukemia

A 6‐year‐old male presented with a testicular mass, hepatosplenomegaly, and a pleural effusion while undergoing maintenance chemotherapy for treatment of T‐cell acute lymphoblastic leukemia (T‐ALL). He was subsequently diagnosed with a lymphoproliferative disorder that resembled hepatosplenic lymphoma (HSL). While the extranodal presentation and the protracted yet aggressive clinical course are consistent with HSL, the findings of monosomy 8 and polymorphic cell populations are unique and have not been previously described in this type of lymphoma. Pediatr Blood Cancer 2013; 60: E10–E12. © 2013 Wiley Periodicals, Inc.     

Successful treatment of mature B‐cell lymphoma with rituximab‐based chemotherapy in a patient with Bloom syndrome

This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11‐year‐old male with mature B‐cell lymphoma, had minimal therapeutic response and significant dose‐limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab‐based chemotherapy protocol. This case highlights that the rituximab‐based chemotherapy protocol is an effective and safe treatment alternative for mature B‐cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment.     

Successful treatment with daclizumab of refractory anaplastic lymphoma

Anaplastic large cell lymphoma (ALCL) is a relatively rare and highly malignant form of non‐Hodgkin lymphoma (NHL) which accounts for 10–15% of these childhood lymphomas. Current treatment protocols for ALCL in children consist of a short course of high intensity polychemotherapy. Here we describe an 8‐year‐old female with relapsed ALCL who achieved good response with anti‐CD25 monoclonal antibody daclizumab. Daclizumab appears to offer a safe treatment option, but further research needs to be conducted in order to define its role in children with ALCL who do not respond to intensive chemotherapy. Pediatr Blood Cancer 2009;53:1130–1131. © 2009 Wiley‐Liss, Inc.     

Pediatric B‐Cell Lymphoma With Lymphoblastic Morphology,TdT Expression,MYC Rearrangement,and Features Overlapping With Burkitt Lymphoma

Burkitt lymphoma (BL) and B‐lymphoblastic lymphoma are subtypes of pediatric non‐Hodgkin lymphoma with different presenting features, treatment, and outcomes. This case report documents a 5‐year‐old female who presented with B‐cell lymphoma with lymphoblastic morphology, terminal deoxynucleotidyl transferase expression, MYC rearrangement, and features overlapping with BL. Genomic microarray analysis identified a gain on the long arm of chromosome 1 without other definitive changes. She was treated according to a BL protocol and remains in remission 16‐months after initial diagnosis.     

Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: a population-based analysis of the Austrian Cooperative Study Group

BACKGROUND: Children and adolescents with Non-Hodgkin lymphoma (NHL) and mature B-cell leukemia (B-ALL) have an excellent prognosis with contemporary chemotherapy stratified according to the histologic subtype and clinical stage of disease. However, a small subset of patients does not respond to front-line therapy or suffers from an early relapse. PROCEDURE: A retrospective analysis was performed to assess the incidence, treatment, and outcome of all children with relapsed or progressed NHL and B-ALL diagnosed in Austria between 1986 and 2003 (n = 22/234). RESULTS: Nine of 140 (6.5%) patients with B-cell NHL/B-ALL (relapse, n = 6; progress, n = 3) failed initial treatment. Four of them underwent a hematopoietic stem cell transplantation (HSCT) as second-line therapy, two patients received intensive chemotherapy alone and in three patients treatment was palliative. Eight of the nine patients died of their disease. Four of 65 (6%) patients with lymphoblastic lymphoma (LBL) (relapse, n = 2; progress, n = 2) had a treatment failure. High-dose chemotherapy followed by HSCT was performed in two of the four patients; another two patients received chemotherapy alone. Three of the four patients died of resistant disease. Nine of 29 (31%) patients with anaplastic large cell lymphoma (ALCL) (relapse, n = 7; progress, n = 2) failed first-line therapy. Six underwent a HSCT (autologous, n = 3; allogeneic, n = 3) and are currently in second complete remission. Treatment of the other three patients consisted of chemotherapy alone-they all died of tumor progression. CONCLUSIONS: Conclusively, patients with early relapsed and progressive B-cell neoplasia or LBL have a very poor prognosis with current treatment approaches, while those with ALCL have a respectable chance to achieve a sustained complete second remission with high-dose chemotherapy and HSCT.