Use of cardiac radiation therapy as bridging therapy to CAR-T for relapsed pediatric B-cell acute lymphoblastic leukemia.

The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with B-ALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CAR-T infusion. Using this approach, he successfully tolerated CAR-T with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in B-ALL.

New attempts for central nervous infiltration of pediatric acute lymphoblastic leukemia.

The cure rate of acute lymphoblastic leukemia (ALL), the commonest childhood cancer, has been sharply improved and reached almost 90% ever since the central nervous system (CNS)-directed therapy proposed in the 1960s. However, relapse, particularly in the central nervous system (CNS), is still a common cause of treatment failure. Up to now, the classic CNS-directed treatment for CNS leukemia (CNSL) has been aslant from cranial radiation to high-dose system chemotherapy plus intrathecal (IT) chemotherapy for the serious side effects of cranial radiation. The neurotoxic effects of chemotherapy and IT chemotherapy have been reported in recent years as well. For better prevention and treatment of CNSL, plenty of studies have tried to improve the detection sensitivity for CNSL and prevent CNSL from happening by targeting cytokines and chemokines which could be key factors for the traveling of ALL cells into the CNS. Other studies also have aimed to completely kill ALL cells (including dormant cells) in the CNS by promoting the entering of chemotherapy drugs into the CNS or targeting the components of the CNS niche which could be in favor of the survival of ALL cells in CNS. The aim of this review is to discuss the imperfection of current diagnostic methods and treatments for CNSL, as well as new attempts which could be significant for better elimination of CNSL.

Intravascular Colonization of Kaposi Sarcoma: Expanding the Spectrum of Specific Infiltrates of B-Cell Chronic Lymphocytic Leukemia.

B-cell chronic lymphocytic leukemia (CLL), a low-grade malignancy consisting of CD5(+), CD23(+), and CD43(+) small B lymphocytes, is the most frequent leukemia in the western world. Patients with CLL may exhibit skin changes characterized by histopathologic evidence of infiltration by atypical B lymphocytes, also known as "specific cutaneous infiltrates of CLL"; in addition, CLL is known to be associated with an increased risk of second cancers, including Kaposi sarcoma (KS). The combination of KS and CLL within the same cutaneous biopsy specimen has only rarely been described. We report a peculiar case of KS occurring in a patient with CLL, in which histopathological evaluation of KS lesions revealed prominent accumulation of CLL lymphocytes within neoplastic vascular spaces. We believe that our findings represent a novel example of intravascular colonization of vascular neoplasms by neoplastic lymphoid cells, further expanding the evergrowing spectrum of specific cutaneous infiltrates of CLL.

The effectiveness of radiotherapy for leukemia cutis.

BACKGROUND: Leukemia cutis (LC) is a rare clinical presentation of leukemia that is associated with poor prognosisabs. To date, the value of radiotherapy (RT) for the treatment of LC remains controversial. Therefore, the aim of this study was to analyse the effectiveness of various RT doses for LC. METHODS AND MATERIALS: Between January 2000 and January 2016, 13 patients underwent RT at our institution after exhibiting progressive disease following other treatment modalities. RESULTS: A total of 36 radiation courses were administered to 13 patients (8 females, 5 males) with a median age of 41 years (range 2-76). Radiation modalities included 32 focal treatments, while total skin electron beam therapy was applied to four patients. The median RT dose was 27 Gy (range 8-34). A complete response rate (CRR) to RT was achieved for 32/36 (89%) lesions (100% for AML lesions versus 33% for the other leukemias; P < 0.001). The median duration of local control (DOLC) for the entire cohort was 38 months (range 0-98), while the median survival (MS) from the time of LC presentation was 13 months (range 2.5-106). The CRR for the LC lesions treated with high-dose regimens (>26 Gy) versus low-dose regimens (≤26 Gy) was 95 versus 83%, respectively (P = 0.26), and the median DOLC was 44 months versus 10 months, respectively (P = 0.019). AML patients had a better long-term outcome than the other patients according to median DOLC (40 months versus 2 months, respectively; P < 0.001) and MS (24 versus 6 months, P = 0.004). RT was well tolerated without significant adverse events. CONCLUSION: A radiation dose ≤26 Gy confer a comparable CRR to high-dose regimens and appears to be an effective treatment for controlling LC progression. However, radiation doses >26 Gy were associated with a longer DOLC. LC patients with underlying AML are associated with better outcome compared with other types of leukemia.

Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission. / Infiltración leucémica y retinitis por citomegalovirus en paciente con leucemia linfoblástica aguda tipo T en remisión completa.

CLINICAL CASE: A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. DISCUSSION: Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases.

Clinical outcome and efficacy of current anti-leukemic therapy for leptomeningeal involvement in acute myeloid leukemia.

We investigated risk factors and outcome in acute myeloid leukemia (AML) patients with leptomeningeal involvement. Medical records of patients with non-promyelocytic AML at Seoul National University Hospital from January of 2000 to November of 2013 were reviewed. Leptomeningeal involvement was defined as the presence of atypical or malignant hematopoietic cells in the cerebrospinal fluid. Among 775 patients with AML, 141 patients (18.2 %) underwent cerebrospinal fluid examination. Leptomeningeal involvement of AML, confirmed in 38 patients (4.9 %), was associated with high white blood cell count and high level of lactic. There were seven patients in the favorable risk group (19.4 %), 21 in the intermediate risk group (58.3 %), and eight in the adverse risk group (22.2 %). Twenty-eight patients (85.7 %) developed leptomeningeal involvement during relapse status or refractory status. Thirty-one patients (81.6 %) received intrathecal chemotherapy, and whole-brain and/or craniospinal radiotherapy was conducted in 10 patients (27.0 %). The rate of complete remission after induction chemotherapy was 63.2 %. Median overall survival was 9.9 months. Radiotherapy and complete remission after the first induction chemotherapy were associated with longer overall survival. Leptomeningeal involvement in acute myeloid leukemia is rare, but relatively common in relapsed status or refractory status. Craniospinal radiotherapy and complete remission after induction chemotherapy were found to favorable prognostic factors.

Therapies on the horizon for childhood acute lymphoblastic leukemia.

PURPOSE OF REVIEW: The prognosis for children with the most common childhood malignancy, acute lymphoblastic leukemia (ALL), has improved dramatically. However, the burden of therapy can be substantial, with long-term side-effects, and certain subgroups continue to have a poor outcome. RECENT FINDINGS: The recent discovery of new genetic alterations in high-risk subsets provides targets for precision medicine-based interventions using existing Food and Drug Administration approved agents. Novel immunotherapeutic approaches are being deployed in relapsed ALL, one of the leading causes of cancer cell death in children. Moreover, genomic analysis has charted the evolution of tumor subclones, and relapse-specific alterations now provide a mechanistic explanation for drug resistance, setting the stage for targeted therapy. There is greater recognition that host factors - genetic polymorphisms - influence cancer risk, response to therapy, and toxicity. In the future, it is anticipated that they will be integrated into clinical decision making to maximize cure and minimize side-effects. Recent efforts to limit prophylactic central nervous system irradiation have been successful, thereby sparing many children late neurocognitive impairments. SUMMARY: Integration of advances in precision medicine approaches and novel agents will continue to increase the cure rate and decrease the burden of therapy for childhood ALL.

Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis.

Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodies were conspicuous on biopsy and may serve as a morphologic clue to lymphocytic differentiation while molecular and immunophenotypic studies are pending. The patient was successfully treated with local radiation therapy and oral ponatinib.

Unilateral optic disk edema with central retinal artery and vein occlusions as the presenting signs of relapse in acute lymphoblastic leukemia.

CLINICAL CASE: A 39-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (LAL Ph+) developed progressive vision loss to no light perception in his right eye. He had optic disk edema and later developed central artery and vein occlusions. Pan-photocoagulation, as well as radiotherapy of the whole brain were performed in several fractions. Unfortunately the patient died of hematological relapse 4 months later. DISCUSSION: Optic nerve infiltration may appear as an isolated sign of a leukemia relapse, even before a hematological relapse occurs. Leukemic optic neuropathy is a critical sign, not only for vision, but also for life, and radiotherapy should be immediately performed before irreversible optic nerve damage occurs.

Bilateral infiltrative disease of the extraocular muscles: a rare clinical presentation of early stage chronic lymphocytic leukemia.

Orbital involvement in chronic lymphocytic leukemia (CLL) is highly unusual and most commonly involves hemorrhage or soft tissue infiltration in advanced disease. We report a case of rapid onset bilateral orbital muscle infiltration as the presenting feature of early stage CLL. In addition, we demonstrate clinico-pathological correlation with an identical chronic B-cell lymphocytic infiltrate in both orbit and bone marrow, with good response of the orbital disease to local radiotherapy.

Allogeneic hematopoietic cell transplantation in children with relapsed acute lymphoblastic leukemia isolated to the central nervous system.

Allogeneic hematopoietic cell transplantation (HCT) is the standard of care for pediatric patients with early medullary relapse of acute lymphoblastic leukemia (ALL). Most patients with isolated central nervous system (CNS) relapse have good outcomes when treated with intrathecal and systemic chemotherapy followed by irradiation to the neuroaxis. However, the role of HCT remains unclear for those patients with early isolated CNS relapse (<18 months) or who had high risk disease at diagnosis. We therefore compared the HCT outcomes of 116 children treated at the University of Minnesota from 1991 to 2006 with relapsed ALL involving the CNS alone (CNS, n = 14), the bone marrow alone (BM, n = 85), or both bone marrow and CNS (BM + CNS, n = 17). There were no significant differences among groups in age at diagnosis or transplant, length of first complete remission (CR1), remission status (CR2 versus >or=CR3), graft source, or preparative regimen. The incidence of acute GVHD was similar between groups. Patients with isolated CNS relapse had the lowest cumulative incidence of mortality following transplant (CNS: 0%, BM: 19%, BM + CNS: 29%, P = .03) and relapse (CNS: 0% BM: 30%, BM + CNS: 12%, at 2 years, P = .01) and highest leukemia-free survival (CNS: 91%, BM: 35%, BM + CNS: 46%, P < .01) at 5 years. Risk factors for poor survival were: T cell leukemia or BCR-ABL gene rearrangement, history of marrow relapse, and receipt of HLA-mismatched marrow. These data support the use of allogeneic HCT in the treatment of children with poor prognosis isolated CNS relapse.