Outcomes after Allogeneic Stem Cell Transplantation for Patients with Non-Hodgkin Lymphoma: Texas Children's Hospital Experience 1999-2013
Swati NaikPaul CastilloCaridad MartinezKathryn LeungGhadir SasaStephen GottschalkNabil AhmedCarl E. AllenRobert A. KranceMalcolm K. BrennerHelen E. Heslop
0
Citation
0
Reference
10
Related Paper
Abstract:
Despite significant improvement in outcomes for patients with pediatric non-Hodgkin lymphomas (NHL), relapsed disease is associated with poor long-term survival. Hematopoietic stem cell transplant (HSCT) is used to improve outcome in this setting but there are limited data in pediatric patients with NHL. We now report on 29 pediatric patients who underwent allogeneic HSCT at our institute between 1999-2013. There were 16 male and 13 female patients and the median age was 14 years (range 5-23 years). Histological categories were anaplastic large cell lymphoma (ALCL) (n=9), lymphoblastic lymphoma (LL) (n=8), diffuse large B cell lymphoma (DLBCL) (n=7), other B cell lymphomas (Burkitt's lymphoma=1, Small cell, non-Burkitt's high grade lymphoma=1, and T-cell rich, B-cell lymphoma=1), and other T-cell lymphoma (Stem cell myeloproliferative/T-cell lymphoma=1, and hepatosplenic T-cell lymphoma=1). 9 patients received grafts from matched-related donors, 8 from matched-unrelated donors, 8 from mismatched-unrelated donors and 4 from haploidentical donors. 21/29 received a myeloablative conditioning regimen (MAC) while 8/29 patients received a reduced intensity conditioning regimen (RIC). At the time of transplant, 23/28 patients were in complete remission (CR=10) or partial remission (PR=13), while 5/28 patients had persistent or progressive disease based on standard established criteria. The 3–year relapse free survival (RFS) was 59% (95%CI: 37%-75%). The overall outcomes varied based on the subtype of lymphoma: patients with ALCL had the best outcomes (9/9 patients are alive and disease free) while those with LL had the worst (1 /8 patients is alive and disease free). Relapsed/progressive disease was the cause of death for all 7 of the LL patients who died. Patients with other B-cell and T-cell lymphomas also fared well (4/7 with DLBCL and 2/3 other B-cell lymphomas and 2/2 other T-cell lymphomas are alive and disease free). Patients in CR or PR had a better OS (18/23) compared with those patients with persistent or progressive disease at time of transplant (0/5). 11/29 patients died (9 from relapse and 2 from treatment related mortality). HSCT offers the possibility of cure for patients with NHL, especially for patients with ALCL and for those patients that have a good response to re-induction therapy prior to transplant. Relapsed disease post-transplant remains a major challenge for patients with LL and for patients transplanted with non-responsive disease. Post transplant therapies to target residual disease should be evaluated in these patients.Keywords:
Lymphoblastic lymphoma
Anaplastic large-cell lymphoma
Regimen
We demonstrate that the expression of TRAF1 and activated c-Rel, two proteins that function in signaling events downstream of activated CD30 in Reed-Sternberg cells, reliably distinguish classical Hodgkin lymphoma from anaplastic large cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and nonmediastinal diffuse large B-cell lymphoma. By immunohistochemistry, we found strong TRAF1 staining in 21 of 25 cases of classical Hodgkin lymphoma. In contrast, strong TRAF1 staining was present in only 1 of 17 cases of anaplastic large cell lymphoma, 0 of 15 cases of lymphocyte predominant Hodgkin lymphoma, and 2 of 36 cases of nonmediastinal diffuse large B-cell lymphoma. Nuclear staining for c-Rel, a pattern consistent with NFκB activation, was observed in the Reed-Sternberg cells in 23 of 25 cases of classical Hodgkin lymphoma but only in 1 of 15 cases of anaplastic large cell lymphoma and 3 of 15 cases of nodular lymphocyte predominant Hodgkin lymphoma. A heterogeneous pattern of subcellular c-Rel localization was found in nonmediastinal diffuse large B-cell lymphoma. Taken together, the combination of strong cytoplasmic TRAF1 expression and nuclear c-Rel was present in 80% of cases of classical Hodgkin lymphoma (n = 25) but in only 3% of cases of the other malignant lymphomas tested (n = 62). Thus, the differential expression patterns of downstream components in the CD30 signaling pathway may prove a useful adjunct in distinguishing cases of classical Hodgkin lymphoma from other malignant lymphomas in routine clinical practice.
Classical Hodgkin lymphoma
Cite
Citations (49)
Lymphoblastic lymphoma
Cite
Citations (30)
High-grade non-Hodgkin's lymphomas generally refer to immunoblastic lymphoma, lymphoblastic lymphoma, and small-noncleaved-cell lymphoma, three histological subtypes that were associated with the worst prognosis at the time of categorization 16 years ago in the Working Formulation for Clinical Usage. Small-noncleaved-cell lymphoma was classified further into Burkitt's lymphoma and non-Burkitt's lymphoma. The treatment of high-grade lymphomas in adults remains somewhat unfavorable today. In children, however, survival rates of 80% to 90% are being achieved with intensive short duration protocols. In this article, the management of Burkitt, Burkitt-like, and lymphoblastic lymphomas is discussed as is the possibility of improved survival in adults using treatment strategies developed for pediatric patients.
Lymphoblastic lymphoma
Cite
Citations (17)
We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP) after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.
Lymphoblastic lymphoma
Hematology
Cite
Citations (3)
Non-Hodgkin’s lymphoma of the breast is extremely rare. Most of these lymphomas are type B, including large B cell diffuse lymphoma, extra-nodal marginal lymphoma, follicular lymphoma, primary effusion lymphoma and lympho-plasma-cytic lymphoma. BIA-ALCL is negative anaplastic lymphoma kinase (ALK) and is characterized by cells with horseshoe-shaped eccentric nuclei called “hallmark cells”. Unlike other types of ALCL, BIA-ALCL rarely invades your breast in depth. By contrast, non-Hodgkin’s T-cell lymphoma (NHL) found in breasts without implants is mostly B cell lymphoma. Due to the increasing number of cases and the fact that the first case also appeared in Romania, we consider it advisable to take information and prevention measures as well as to adopt a treatment protocol in our country. The present paper aims at adopting a unitary diagnosis and treatment protocol for all plastic surgeons. We also consider it advisable to inform patients before surgery on risk. Through this paper we want to propose a national protocol to follow and also to argue its choice.
Anaplastic large-cell lymphoma
Follicular lymphoma
T-Cell Lymphoma
Large cell
Cite
Citations (2)
Objective To evaluate the clinical and pathological features of childhood non-Hodgkin's lymphoma(NHL).Methods A total of 195 NHL cases,with age younger than twelve years old,diagnosed from January 1982 to January 2010 in Xinhua Hospital were reviewed.Results The peak onset age is 6-8 years old.The male to female ratio is 2.3 ∶ 1 and male patients predominate in each subtype.The cases in stage Ⅲ and Ⅳ account for 49.2%.The most common subtypes were lymphoblastic lymphoma(LBL),Burkitt lymphoma(BL)and anaplastic large cell lymphoma(ALCL).About 88.8% cases of LBL is T-cell lymphoma while all the BL is B-cell lymphoma and all the ALCL is T-cell lymphoma.More than 1/3(37.9%)of all the cases have primary extranodal lymphoma.More than one organ involvement was found in 56.1% of LBL cases when they were diagnosed.Conclusions Childhood NHL differs greatly from adult NHL in clinical and pathological aspects.Immunohistochemistry plays an important role in diagnosis.
Lymphoblastic lymphoma
Anaplastic large-cell lymphoma
Large cell
Cite
Citations (0)
Objective To analyze the clinicopathological features of childhood lymphoma.Methods Seventy-five cases of childhood lymphoma were selected from the files in period of 1996 to 2009 year.Pathologic diagnosis and immunophenotype analysis were performed according to the WHO classification for tumors of hematopoietic and lymphoid tissue(2008).Fluorescence in situ hybridization(FISH) were used for detection of the segregation of c-myc gene in Burkitt lymphoma tumor and diffuse large B-cell lymphoma tumor.Results There were 57 cases of male and 18 cases of female in 75 cases of childhood lymphoma,the ration of sex was 3.171,the average age was 8.74 years old.There were 32 cases(42.7%) in lymph node,43 cases(57.3%) in extra-node,there were more cases(29.3%) in gastrointestinal tract.The most common subtypes were Hodgkin lymphoma(13 cases,17.3%),lymphoblastic lymphoma(16 cases,21.3%),anaplastic large cell lymphoma(12 cases,16.0%),Burkitt lymphoma and diffuse large B-cell lymphoma(33 cases,44.0%),small lymphocytic lymphoma(1 case,1.3%).The genetic change of c-myc gene was executived by FISH in cases of Burkitt lymphoma tumor and diffuse large B-cell lymphoma tumor.Eighteen cases of Burkitt lymphoma tumor existed the c-myc gene segregation in 28 cases of Burkitt lymphoma and diffuse large B-cell lymphoma.Conclusions These cases of male are more than those of female.There are more cases in lymph node and gastrointestinal tract.The most common subtypes are Burkitt lymphoma,lymphoblastic lymphoma,Hodgkin lymphoma,anaplastic large cell lymphoma and diffuse large B-cell lymphoma.
Lymphoblastic lymphoma
Anaplastic large-cell lymphoma
Immunophenotyping
Large cell
Cite
Citations (0)
Lymphoblastic lymphoma
T-Cell Lymphoma
Cite
Citations (5)
Thirty patients under 20 years of age with non-Hodgkin's lymphoma, with nodal and extranodal involvement, were reviewed retrospectively according to Rappaport's classification. All cases had a diffuse histologic pattern. There were 10 patients with lymphoblastic lymphoma (nine with convoluted nuclei and one with non-convoluted nuclei), 10 with Burkitt's lymphoma, six with undifferentiated lymphoma, and four with histiocytic lymphoma. Histochemistry was done in 28 cases, and electron microscopy in three. Twenty-four patients were male and six were female; ages at presentation ranged from 3 to 19 years. Nine patients with lymphoblastic lymphoma (with convoluted nuclei) and two with Burkitt's lymphoma had a mediastinal mass at diagnosis. Three patients with Burkitt's lymphoma and one with undifferentiated lymphoma had bone marrow involvement initially. Leukemic transformation occurred in four patients with lymphoblastic lymphoma within a year of diagnosis. Initial treatment included radiotherapy alone in three patients, chemotherapy alone in three patients, and combined radiotherapy and chemotherapy in 24 patients. Thirteen patients have died at 2 to 52 months from diagnosis: five of 10 with lymphoblastic lymphoma, three of 10 with Burkitt's lymphoma, four of six with undifferentiated lymphoma, and one of four with histiocytic lymphoma. Our findings suggest that in this patient population, non-Hodgkin's lymphoma can be classified using Rappaport's criteria and that malignant lymphomas of the lymphoblastic type and undifferentiated lymphoma seem to have the worst prognosis.
Lymphoblastic lymphoma
Burkitt's lymphoma
Cite
Citations (36)
Lymphoblastic lymphoma (LBL) and Burkitt's lymphoma belong to the very aggressive lymphomas requiring intensive therapy. We retrospectively analyzed 29 patients with Burkitt's lymphoma and 29 patients with LBL who received induction therapy with a CHOP-like lymphoma protocol. Patients with Burkitt's lymphoma (with a median age of 54.5 years) have a CR rate of 72% and a lymphoma free long-time survival of 55%. The International Prognostic Index was the most valuable prognostic factor for survival. Patients with LBL with a median age of 45 years had a CR rate of 55% and a lymphoma-free survival of 38%. Stage was the most predictive prognostic factor. Our data suggest that for older patients (>50) treatment with lymphoma protocols may yield response rates that are comparable to the results of patients with disseminated diffuse large cell lymphoma. Younger patients with risk factors should be treated with more intensive therapy like ALL-protocols. The role of auto-transplantation after high dose therapy (HDT) however as part of primary treatment still needs to be evaluated in clinical trials. One of four patients with LBL who received HDT and one of four patients with Burkitt's lymphoma who received HDT achieved long-term remission.
Lymphoblastic lymphoma
International Prognostic Index
Burkitt's lymphoma
Cite
Citations (42)