Extramedullary Relapse Of Acute Lymphoblastic Leukemia Research Articles

Leukemic Optic Neuropathy: A Harbinger of Relapse in Acute Lymphoblastic Leukemia

Background: Leukemic infiltration of the optic nerve is a neuro-oncologic emergency and also a sign of extramedullary central nervous system relapse. It presents a clinical dilemma in the early stages due to multiple differentials. Patients with leukemia receive radiation and chemotherapy are thus, susceptible to inflammatory, toxic, and infectious causes of optic neuropathy, besides infiltration with tumor cells. Clinical Description: A 15-year-old boy treated for acute lymphoblastic leukemia (ALL) and in remission for 7 months, presented with the unilateral decreased vision for 7 days. A structured evaluation was done, comprising visual acuity, color vision, field of vision, fundus, ophthalmoscopy, ultrasound b-scan, and magnetic resonance imaging of the orbit. The final diagnosis was leukemic infiltration of the optic nerve. Cerebrospinal fluid (CSF) analysis confirmed the presence of atypical lymphocytes. Management: The patient was diagnosed with extramedullary relapse of ALL. Since there are no standard guidelines, a literature review was performed, and the treating team decided to start the patient on stand-alone chemotherapy. Symptomatic resolution became apparent within 10 days. On follow-up, the optic nerve lesion resolved with residual gliosis in the surrounding retina. The CSF has become clear, and the patient is now considered to be in remission. Conclusion: It is important to use a structured clinical approach coupled with investigations to recognize the ocular involvement of ALL (especially in younger patients). There is a need for a regular routine ophthalmological examination in patients in remission for early detection of a relapse. There is a strong felt need for pediatric hemato-oncologists to plan research in this area to generate data so that recommendations for the management of extramedullary relapses are formulated.

Adequate asparaginase is important to prevent central nervous system and testicular relapse of pediatric Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukemia

Asparaginase (Asp) is one of the most important drugs for treating acute lymphoblastic leukemia (ALL). However, off-protocol Asp administration (OPAA) or hypersensitivity may disturb its pharmacokinetic profile. In this retrospective study, we sought to determine whether OPAA and hypersensitivity to Escherichia coli asparaginase (E. coli Asp) impaired extramedullary relapse prevention in a pediatric ALL cohort treated according to SCMC-ALL-2005 protocol from 2005 to 2014 at the Shanghai Children's Medical Center (SCMC). In total, 676 patients were enrolled in this study, including 369 with OPAA and 60 exhibiting hypersensitivity to E. coli Asp. At the end of the most recent follow-up, 58 patients had extramedullary relapse. The 5-year cumulative extramedullary relapse incidence in patients with OPAA was 11.01%, whereas that in patients without OPAA was 5.28% (P=.0036). Moreover, the 5-year cumulative extramedullary relapse incidence in patients that exhibited hypersensitivity to E. coli Asp was 16.48%, whereas that in patients without hypersensitivity was 7.59% (P=.0195). Concerning the relapse site, OPAA not only increased central nervous system (CNS) relapse but testicular relapse as well. Based on Fine and Gray multivariate analysis, OPAA and hypersensitivity to Asp were independent risk factors for extramedullary relapse. In conclusion, to prevent extramedullary relapse of ALL, adequate duration to administrate Asp was more important than the total dosage, and more attention should be paid to Asp inadequate due to hypersensitivity. This article is protected by copyright. All rights reserved.

Extramedullary Relapse of Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Different Characteristics between Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia

Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation–based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post–allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed.

Breast tumour as the first manifestation of extramedullary relapse of Philadelphia positive (Ph+) acute lymphoblastic leukemia

Extramedullary relapses of acute lymphoblastic leukemia (ALL) are rare and usually localized in the central nervous system. We describe such an uncommon case of extramedullary relapse of ALL in the breast of a 44 year old female. The patient, who had been diagnosed with precursor B cell, Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) 5 years before and had been in complete molecular remission for the last 19 months, was admitted to the hospital for investigation of a hard, non-tender lump in her right breast. Mammography detected a dense, ill-defined mass, whereas on grey-scale and power Doppler sonography, the appearance of the lesion was consistent with malignancy. Histopathologic and immunohistochemical examination of the specimen demonstrated a similar immunophenotype (CD20+, CD10+, Tdt+, CD3-) as this of the onset ALL cell population in the bone marrow.

Extramedullary Gastric Relapse of Acute Lymphoblastic Leukemia Following Allogeneic Stem Cell Transplant

A 26-year-old man with a prior history of acute leukemia that was treated with a stem cell transplant (SCT) was referred for an F-18 FDG PET/CT to assess suspicious new gastric mucosal lesions. The lesions were FDG-avid and were histologically proven to be acute lymphoblastic leukemia (ALL). Extramedullary relapse of ALL after SCT is very rare, with only 60 cases reported in the literature, and the role of F-18 FDG PET/CT in monitoring for ALL relapse following SCT has not been previously investigated. This rare case report highlights the use of F-18 FDG PET/CT in staging gastric relapse of ALL following SCT.

Extramedullary relapse of acute lymphoblastic leukemia in childhood to the prostate

A 6-year-old boy presented with the chief complaints of miction pain and pollakisuria. He had a past history of acute lymphoblastic leukemia (ALL), which subsided in response to chemotherapy at 3 years of age. Ultrasonography revealed urinary retention associated with bilateral hydronephrosis secondary to the prostate enlargement. Computed tomography and magnetic resonance imaging showed no other abnormal finding. Transrectal needle biopsy showed infiltration of leukemic cells in the prostate. Bone marrow puncture and cerebrospinal fluid aspiration revealed no leukemic cells, resulting in a diagnosis of extramedullary relapse of ALL in the prostate. Although he was successfully treated by chemotherapy, irradiation and his voiding function was improved, ALL relapsed in the left testis 1 year later. In spite of left orchiectomy, irradiation and additional chemotherapy, he died of bone marrow relapse and multiple organ failure. Extramedullary relapse of ALL in the prostate is very rare. To our knowledge, our case is the first well-documented report in the published work.

Prognostic Impact of MRD in the Bone Marrow of Children at First Isolated Extramedullary Relapse of ALL.

Sensitive quantification of minimal residual disease (MRD) is an established method to assess treatment response in patients with bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL). We have investigated, whether MRD can also determine the tumor load in the BM at cytologically isolated extramedullary (IEM) relapse and can consequently be associated with prognosis in this subgroup.The extent of sub-cytological BM involvement at relapse diagnosis has been quantified in 53 patients with first relapse in the central nervous system (n=36), and in the testes (n=17) treated in Germany (n=33; 09′94 - 12′03) and Czech Republic (n=9; 10′01 - 04′04), or in France (n=11; 12′90 - 11′03) according to protocols ALL-REZ BFM, or to COOPRALL, respectively. MRD has been sensitively assessed by real-time-quantitative PCR using T-cell-receptor and immunoglobulin gene-rearrangements detected in the extramedullary or initial BM material. Stability of initial clonal markers was confirmed. A MRD-level of <10−4 was measured in 22 patients. Thirty-one patients showed a positive MRD-status: <10−3 - =/>10−4: n=9; <10−2 - =/>10−3: n=12; and >10−2: n=10. MRD-status was not associated with the relevant prognostic parameters sex, time-point of relapse, immunophenotype, and site, whereas it was associated with age at initial diagnosis (p=.057), and BCR/ABL translocation (p=.011). The probability of event-free survival (EFS) at 5 years was .55+/−.15 and the rate of subsequent relapses was 18% in patients without MRD detection at a level of 10−4 compared to .16+/−.10 and 52% in those with =/>10−4 (p(log-rank)=.16 and p=.028 respectively).Our study reveals a large range of subcytological BM involvement in patients with IEM relapses of ALL. A relation to single prognostic factors and to the relapse rate can be found, but not to EFS.The study was kindly supported by ‘Deutsche Kinderkrebsstiftung', Germany, by ‘Kompetenznetz der Paediatrischen Onkologie', BMBF, Germany; by ‘programme hospitalier de recherche clinique' (PHRC 2002), France and by GAUK 62/2004, Czech Republic.

Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation

A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart.