Persistent Multiyear Control of Relapsed T‐Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report

There are few therapeutic options for patients with T‐cell acute lymphoblastic leukemia (T‐ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T‐ALL. We present the case of a now 9‐year‐old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life.     

Early T‐Cell Precursor Acute Lymphoblastic Leukemia in an Infant With an NRAS Q61R Mutation and Clinical Features of Juvenile Myelomonocytic Leukemia

Early T‐cell precursor acute lymphoblastic leukemia (ETP‐ALL) is a subtype of T‐acute lymphoblastic leukemia (T‐ALL) arising from a primitive precursor. We present a unique case of an infant with ETP‐ALL with a missense NRAS mutation in codon 61 (c.182A>G, p.Q61R). The patient also had a minor population of non‐ETP T‐ALL blasts and clinical features typically associated with juvenile myelomonocytic leukemia (JMML), namely, absolute monocytosis, splenomegaly, and elevated hemoglobin F. The treatment was initiated with chemotherapy, followed by cord blood transplantation. The patient achieved remission, but unfortunately died from transplant‐related complications. This case highlights an NRAS mutation in ETP‐ALL with JMML‐like phenotype.     

Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

A pediatric patient diagnosed initially with B‐lymphoblastic leukemia (B‐ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T‐cell (CAR‐T) therapy and hematopoietic stem cell transplant. A TCF3‐ZNF384 fusion was identified at diagnosis, persisted through B‐ALL relapse, and was also present in the AML relapse cell population. ZNF384‐rearrangements define a molecular subtype of B‐ALL characterized by a pro‐B‐cell immunophenotype; furthermore, ZNF384‐rearrangements are prevalent in mixed‐phenotype acute leukemias. Lineage switch following CAR‐T therapy has been described in patients with KMT2A (mixed lineage leukemia) rearrangements, but not previously in any patient with ZNF384 fusion.     

Next‐generation sequencing of PTEN mutations for monitoring minimal residual disease in T‐cell acute lymphoblastic leukemia

Minimal residual disease (MRD) analysis has become a powerful indicator to refine therapy in acute lymphoblastic leukemia (ALL). Here, we present an MRD detection based on the next‐generation sequencing of PTEN exon 7 mutations (NGS‐PTEN) in 30 pediatric T‐cell ALL patients. By comparing the NGS‐PTEN results with current quantitative PCR of antigen receptor gene rearrangements (qPCR‐Ig/TR), an overall concordance of 80% was found between the two methods. However, the NGS‐PTEN qualified a lower number of high‐risk patients than qPCR‐Ig/TR. These findings suggest that NGS‐PTEN is a promising tool that could potentially be used to support current MRD methodologies for T‐ALL patients.     

Chimeric antigen receptor T‐cell therapy in patients with neurologic comorbidities

Chimeric antigen receptor T cells (CAR‐T) are an effective and potentially durable treatment for refractory and multiply relapsed B‐cell acute lymphoblastic leukemia. Neurotoxicity is frequent after CAR‐T cell therapy. Mechanisms driving neurotoxicity are incompletely understood, and symptoms can range from transient and mild to severe and life‐threatening. Providers have exercised caution in providing CAR‐T to patients with neurological comorbidities or extramedullary disease. Here, we report three patients with prior significant neurologic morbidity who safely tolerated CAR‐T cell infusion after bridging therapy with conventional chemotherapy.     

Evidence for BCR/ABL1‐positive T‐cell acute lymphoblastic leukemia arising in an early lymphoid progenitor cell

BCR‐ABL1‐positive leukemias have historically been classified as either chronic myelogenous leukemia or Ph+ acute lymphoblastic leukemia. Recent analyses suggest there may be a wider range of subtypes. We report a patient with BCR‐ABL1 fusion positive T‐cell ALL with a previously undescribed cell distribution of the fusion gene. The examination of sorted cells by fluorescence in situ hybridization showed the BCR‐ABL1 fusion in the malignant T cells and a subpopulation of the nonmalignant B cells, but not nonmalignant T cells or myeloid or CD34+ progenitor cells providing evidence that the fusion may have occurred in an early lymphoid progenitor.     

The response of bovine beta‐lactoglobulin‐specific T‐cell clones to single amino acid substitution of T‐cell core epitope

Cow’s milk is one of the most common food allergens in the first year of life, with approximately 2.5% of infants experiencing an allergic reaction to it. Beta‐lactoglobulin (BLG) is one of the major allergens in cow’s milk. Previously, we reported that four of six T‐cell clones (TCC) which were established from cow’s milk allergy patients recognized BLGp97‐117 as the core sequence and also recognized BLG in association with the human leucocyte antigen (HLA)‐DRB1*0405 allele. Using two of these four TCCs, we evaluated the T‐cell response to BLG peptides with single amino acid substitution or deletion and identified BLGp102‐112 as the minimum essential region in BLGp97‐117. In the alanine‐scan assay, the proliferative responses of TCCs to pE108A disappeared, and the proliferative responses of TCCs to pC106A decreased. In the analog peptide proliferation assay, pY102S had retained some T‐cell response to the two TCCs. Collecting these results, we propose a motif for the interaction between the HLA‐DRB1*0405 allele and antigen peptide, and suggest that BLGp105‐108 are important residues to retain the TCR/BLG‐peptide/HLA complex. pY102A and pY102S are partial agonists for the T‐cell receptor. These peptides might be considered as candidate peptides for the modification of the T‐cell response to BLG in cow’s milk allergy.     

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.     

Spontaneous tumor lysis syndrome in a child with T‐cell acute lymphoblastic leukemia

We report a 5‐year‐old female who presented with unexplained acute renal failure (ARF) and hyperuricemia and who was subsequently diagnosed of T‐cell acute lymphoblastic leukemia (ALL). Peripheral smear was initially unremarkable. She required hemodialysis. Two weeks later, peripheral smear showed 40% blasts and bone marrow demonstrated T‐cell ALL. Our case was the fifth and the youngest case of ALL with spontaneous tumor lysis syndrome. However, in contrast to previous reports in ALL or acute myeloid leukemia, our patient did not have blasts noted on periphereal blood smear and her white blood cell count and serum lactate dehydrogenase level were normal on admission, a time when dialysis‐dependent ARF and severe hyperuricemia were present. Occult hematologic malignancy should be considered in cases of ARF and hyperuricemia of unknown etiology even when peripheral hematologic findings are not informative. Pediatr Blood Cancer 2010;54:773–775. © 2009 Wiley‐Liss, Inc.     

Immunological Classification of Childhood Acute Lymphoblastic Leukemia

Seven hundred and forty-four newly diagnosed patients with acute leukemias between 1978 and 1990 were classified on the basis of immunological phenotypes. The majority of the patients were enrolled in the Tokyo Children's Cancer Study Group (TCCSG) studies. The incidence of subclassification of acute leukemias in this study was as follows: 522 patients with ALL (70%), 139 patients with ANLL (18%), 29 patients with biphenotypic leukemia, 8 patients with Ph1-positive acute leukemia (Ph^-AL), and 45 patients with infant leukemia. ALLs were classified into common ALL (cALL, 77%), T-ALL (15%), B-ALL (4%), and unclassified ALL (3%). The incidence of ALL subtypes in this study reflected those of TCCSG. Biphenotypic leukemias were categorized into 4 groups as follows; 1) cALL with positive myelomonocytic antigen(s) (N = 11), 2) unclassified ALL with positive myelomonocytic antigen(s) (N = 5), 3) ANLL with positive B-lymphoid antigen(s) (N = 4), and 4) acute leukemia with positive T-lymphoid and myeloid antigen(s). Infant leukemias were classified into ALL type (N = 27) and ANLL type (N = 18). In this present study, clinical features and immunological phenotypes of the acute leukemias with a poor prognosis, i.e. biphenotypic leukemia, Ph^-AL, and infant leukemia are analyzed and discussed.