Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia (ALL) at Diagnosis and/or at First Relapse: Results from the GET-LALA Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4326-4326
Author(s):  
Oumedaly Reman ◽  
Arnaud Pigneux ◽  
Francoise Huguet ◽  
Norbert Vey ◽  
Andre Delannoy ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Unrelated Donor ◽  
Cns Involvement ◽  
Cns Disease ◽  
Cns Relapse ◽  
First Relapse ◽  
B Lineage

Abstract Outcome of adult ALL with central nervous system (CNS) involvement is not clearly defined. We studied 104 patients presenting with CNS involvement at diagnosis among 1493 patients (7%) included into the LALA-87 or LALA-94 trials, and 109 patients (9% of first remitters) presenting CNS disease at the time of first relapse among the 709 relapsing patients (15%) included initially in these trials. Treatment of patients presenting CNS involvement at diagnosis consisted in initial chemotherapy completed by 18 double or triple intrathecal injections associated with 15 to 20 Gy cranial irradiation, followed when possible by intensification by allogeneic or autologous stem cell transplantation (SCT). At diagnosis, 43 patients (41%) presenting with CNS involvement had T-lineage ALL, 53 (51%) had B-lineage ALL (of whom 9 were diagnosed as Philadelphia (Ph) chromosome positive ALL), 8 had undifferentiated ALL or unknown immunophenotype. Eighty-seven of 104 (84%) patients with CNS involvement at diagnosis achieved complete remission (CR). Fifty-three patients underwent SCT (25 allogeneic SCT from matched related or unrelated donor, 28 autologous SCT). Overall survival at 7 years was 34% in those with CNS involvement at diagnosis versus 29% (p = NS) for those without. DFS at 7 years was 35% versus 28% (p = NS). There were no significant differences between patients with CNS involvement and those without CNS involvement regarding T lineage ALL, B lineage ALL (including or not Ph ALL). There were also no significant differences regarding patients who underwent transplantation as consolidation intensification, while in patients receiving only chemotherapy patients without initial CNS involvement had a better outcome (p = 0.01). Among the 709 patients with primary relapse, 66 patients (61%) presented a CNS relapse combined with bone marrow relapse, whereas 17 relapses (15%) and 26 relapses (24%) were CNS relapses combined with another extramedullary relapse or isolated CNS relapses respectively. Median time to relapse was 6.7 months (range, 1–62) in patients with CNS relapse versus 11.2 months (1.7–111) in relapsing patients without CNS involvement. Eleven patients (10%) with CNS relapse had CNS involvement at diagnosis, while 98 patients were diagnosed with CNS disease only at the time of first relapse. Overall, 38 out of 109 patients with CNS relapse (35%) achieved CR. The median OS was 6.3 months. Outcome was similar in terms of CR proportion and OS in relapsing patients without CNS involvement. The 2-year OS rates did not show any difference among patients with CNS relapse who had CNS involvement at diagnosis and those with CNS disease only diagnosed at the time of first relapse.Overall, CNS leukemia in adult ALL is uncommon at diagnosis. Patients have a similar outcome than those who did not present with CNS involvement. However, patients benefit from intensification therapy by autologous or allogeneic SCT. CNS leukemia at first relapse are also uncommon but probably underestimated. Outcome is particularly poor as this of all adult ALL in first relapse.

Low Expression of IL-15 in Adult B-Lineage Acute Lymphoblastic Leukemia Is Associated with Central Nervous System Involvement at Initial Presentation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2389-2389
Author(s):  
Shuling Wu ◽  
Thomas Burmeister ◽  
Claudia Baldus ◽  
Stefen Schwartz ◽  
Michael Notter ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Initial Presentation ◽  
Leukemic Cells ◽  
Cns Involvement ◽  
Childhood All ◽  
First Relapse ◽  
B Lineage ◽  
Lower Expression

Abstract The biologic mechanisms of the development of central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is unknown. Risk factors associated with CNS involvement include the immunophenotype (e.g. T-ALL), high white blood cell (WBC) count and cytokine expression. Among the latter, interleukin (IL)-15 has shown to enhance the proliferation of both normal and malignant lymphocytes, thus, suggesting its potential role in leukemogenesis. It has been shown that in childhood ALL, CNS involvement is associated with higher IL-15 expression (Cario et al. 2006, Blood108a:2270). In this study, we analyzed the expression of IL-15 and its alternatively spliced variants in leukemic cells from adult ALL patients with CNS involvement (CNS+) at initial presentation (n=31) and at first relapse (n=8), as well as in patients without CNS involvement at diagnosis (CNS−; n=57). Experiments were performed by real-time RT-PCR and the values were presented ratios comparing IL-15 to expression of the reference gene belta-actin. mRNA expression levels were also correlated with protein expression by western blot analysis. We found that the expression of total IL-15 was significantly lower in ALL patients with CNS+ at initial presentation (n=31, median=0.02, range 0–0.45, P<0.001) and at first relapse (n=8; median=0.03, range 0–0.08, P=0.019), in comparison to ALL patients without CNS (n=57, median=0.08, range 0–0.91). Similarly, lower expression values of IL-15 were found in B-cell precursor (BCP)-ALL (P=0.015) as well as in the subtype of common ALL (p=0.013) with CNS+, as compared to cases without CNS-. In CNS+ ALL, patients with BCR–ABL+–BCP–ALL (n=9) had lower IL-15 expression compared to patients with BCR–ABL–BCP–ALL (n=21, P=0.017). In contrast to CNS– patients, no statistically significant difference was found regarding IL-15 expression between BCR–ABL+- and BCR–ABL–BCP–ALL. Furthermore, the expression of IL-15 was more than 5-fold higher in T–lineage ALL (n=23) than in BCP-ALL (n=72, p<0.001). Among T-lineage-ALLs, CD1+ cortical-T-ALL strongly expressed IL-15 as compared with pre-T or mature T-ALLs. The expression of both spliced variants of long signal peptide (LSP)-IL-15 and short signal peptide (SSP)-IL-15 did not differ between CNS+ and CNS– of all cases. Interestingly, the expression of LSP-IL-15 and SSP-IL-15 is higher in common or pre-B than in pro-B-leukemic cells, whereas high LSP-IL-15 was found in cortical T-ALL, but not in pre-T or mature T-ALL. In conclusion, lower expression of IL-15 in adult BCP-ALL at diagnosis was associated with CNS involvement. This unexpected difference in IL-15 expression between adult and childhood ALL may reflect differences in biologic features of leukemic cells and/or inflammation processes in the pathogenesis of CNS disease. Furthermore, the expression of IL-15 and its spilced variants was correlated with lineage commitment and differentiation status of leukemic cells in B-lineage-ALL as well as in T-ALL. It remains to be evaluated whether these prognostic and biologic findings of distinct expression pattern of IL-15 in adult ALL subtypes will have therapeutical implications for the future antileukemic strategies.

Central nervous system involvement in American Burkitt's lymphoma.

1983 ◽  
Vol 1 (11) ◽  
pp. 677-681 ◽  
Author(s):  
E Sariban ◽  
B Edwards ◽  
C Janus ◽  
I Magrath
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Burkitt’S Lymphoma ◽  
Cranial Irradiation ◽  
Burkitt's Lymphoma ◽  
Cns Involvement ◽  
Cns Disease ◽  
Cns Relapse

Sixty-four patients with American Burkitt's lymphoma (AMBL) treated at the National Cancer Institute were reviewed to determine the frequency and characteristics of central nervous system (CNS) involvement. Patients with minimal or completely resected tumor never had CNS disease. Of the 45 patients with more extensive disease, 15 had CNS disease: nine presented with CNS disease, six of whom subsequently had recurrent CNS disease, and six developed CNS disease only at relapse. There was a significant association between CNS and bone-marrow disease at presentation. Therapy of CNS disease consisted of short courses of intrathecal chemotherapy with cytosine arabinoside and methotrexate. Cranial irradiation was given only to patients with CNS relapse. There are six long-term survivors (LTS) who have been disease free for four to six years post chemotherapy. Of these six LTS, three presented with CNS disease, two experienced isolated CNS relapse, and one had CNS disease both at presentation and at relapse. Three of the six LTS never received cranial irradiation. It is concluded that CNS involvement in AMBL can be effectively treated, and that long-term remission, which is probably cure, can be achieved.

Mitoxantrone Improves the Outcome of Children with Central Nervous System (CNS) Involvement at First Relapse of Acute Lymphoblastic Leukemia (ALL)-Results of the International ALLR3 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3303-3303
Author(s):  
Ashish Narayan Masurekar ◽  
Catriona Anne Parker ◽  
Satarupa Choudhuri ◽  
Carly Leighton ◽  
Jeremy Hancock ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cns Involvement ◽  
Cns Disease ◽  
Off Label ◽  
Cns Relapse ◽  
Time To Relapse

Abstract Abstract 3303 Introduction: Despite improvement in frontline therapy in childhood acute lymphoblastic leukemia (ALL), central nervous system (CNS) relapse remains a significant clinical problem. The ALLR3 trial (ISCRTN 45724312) was designed specifically to address this issue with the use of drugs known to penetrate the CNS. The trial incorporated a randomization between Mitoxantrone and Idarubicin during induction. Mitoxantrone showed an early benefit in all patients resulting in closure of the randomization in December 2007 (ASH Annual Meeting Abstracts, Nov 2009; 114:3390). Subsequently all patients now receive Mitoxantrone. Here we report on the outcome of patients with isolated CNS relapse (iCNSr) or combined CNS relapse (involvement of CNS and bone marrow, cCNSr). Methods: CNS involvement was defined as ≥5 WBC/μl with morphological evidence of blasts in the cerebrospinal fluid (CSF). Combined relapse (cCNSr) was defined as CNS disease with ≥ 5% blasts in the bone marrow. Time to relapse was classified as, Very Early: within 18 months of first diagnosis; Early: after 18 months of first diagnosis but within 6 months of stopping therapy and Late: more than 6 months after stopping therapy. All patients received 3 blocks of chemotherapy. Subsequently, allogenic stem cell transplant (allo-SCT) was offered to all very early relapses (iCNSr & cCNSr), early iCNSr (irrespective of immunophenotype), all T-cell cCNSr (irrespective of time to relapse) and early or late pre-B cCNSr that had a minimal residual disease level of ≥ 104 at the end of induction. All other patients were offered chemotherapy and cranial radiotherapy. Results: Of a total of 330 relapsed patients, 102 (31%) had CNS involvement. Of these 63 (62%) had iCNSr and 39 (38%) had cCNSr. The incidence of CNS disease was higher in males (M:F, CNS relapses 2.5:1 vs all relapses 1.5:1). CNS relapses had a higher proportion of T-cell disease (pre B:T CNS relapses 3.6:1 vs all relapses 7.8:1]. The number of patients presenting in very early, early and late phases were 19 (19%), 55 (54%) and 28 (27%) respectively. All late iCNSr patients were males. Almost all late relapses (iCNSr and cCNSr) (27/28) were of a pre B phenotype. At the end of induction phase, 91/102 (89%) achieved complete remission (CR) and 82/102 (80%) remained in CR after 3 blocks of chemotherapy. The estimated 3-year overall survival (OS) and progression free survival (PFS) for all patients with CNS disease was 45.5% (95%CI 32.9, 58.0) & 43.4% (95%CI 32.0, 54.7) respectively. There were no significant differences in survival with respect to site of the disease (combined vs isolated), gender or immunophenotype (pre B vs T). As shown in Table 1, CNS relapse patients who received Mitoxantrone had a significantly improved outcome when compared to those who received Idarubicin. This was most evident in those who had i) iCNSr, ii) pre-B phenotype and iii) allo-SCT, when analyzed on an intention to treat basis. This represents a considerable improvement in outcome compared to the results obtained in these sub-groups of patients in the previous UK ALLR2 study (Roy A et.al. Br. J. Haem. 2005;130:67-75). Conclusion: Mitoxantrone is highly effective in children with relapsed pre B ALL who have CNS involvement. As there were no other differences between patients treated on Mitoxantrone or Idarubicin, effective systemic therapy is as important as CNS directed therapy, if not more, in treating patients with CNS relapse. Disclosures: Off Label Use: Most drugs used in this protocol are off label as the majority of drugs used in childhood ALL are not liscensed for use in children.

Chemokines in Leukemic Infiltration of the Central Nervous System in Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1627-1627
Author(s):  
Manuel Ramirez ◽  
Ana M Gomez ◽  
Carolina Martinez ◽  
Alvaro Lassaletta ◽  
Jose L Fuster ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Chemokine Receptors ◽  
Lymphoblastic Leukemia ◽  
Cns Disease ◽  
Leukemic Infiltration ◽  
Cns Relapse ◽  
Chemokine Ligands

Abstract Abstract 1627 Poster Board I-653 Background Leukemic blasts from B-cell acute lymphoblastic leukemia (B-ALL) and T-ALL circulate through the blood stream and may infiltrate different organs. Extramedullary organs may act as sanctuaries for lymphoblasts, preventing the exposure to adequate levels of chemotherapeutic drugs. Typical extramedullary relapses are seen in testes and in central nervous system (CNS). We aimed at determining whether chemokines may play a role in the infiltration of the CNS by leukemic blasts in childhood ALL. We studied the expression of chemokine receptors in ALL blasts in marrow, as well as the levels of chemokine ligands in the cerebrospinal fluid (CSF) of children with B- or T-ALL. If chemokines had a role in CNS leukemic infiltration, the following should be confirmed: leukemic blasts should express high levels of the chemokine receptor/s for which high levels of its corresponding ligand/s were detected at the CNS. Methods This prospective study was approved by the local ethical committees for clinical research. Samples from 80 children in 10 Spanish pediatric oncology units were obtained. We detected the presence of leukemic blasts in CFS by flow cytometry. We defined leukemic infiltration of CFS samples as the presence of cells with the same immunophenotype as the leukemia in the marrow aspirates. We detected the expression levels of 9 CCR and 6 CXCR molecules in ALL blasts by flow cytometry in marrow aspirates. Levels of chemokine ligands were quantitated by Cytometric Bead Array or by commercial ELISA kits in CSF samples. Results We found that chemokine receptors expression and levels of chemokine ligands varied depending upon the lineage (T versus B), the maturation state (pre-T versus T; pro-B versus pre-B versus common-B) and the risk-status (high versus non-high) of the leukemia. T-ALL patients with high levels of CNS leukemic infiltration expressed significantly higher levels of CXCL10 compared to the same parameters of T-ALL patients with low/absent levels of CNS disease (p=0,049). Common B-ALL patients with high levels of CNS leukemic infiltration expressed higher levels of CCL22 compared to that of common B-ALL patients with low/absent levels of CNS disease (p=0,059). Among the 4 patients with a CNS relapse, we detected higher levels of CXCR3 (p=0,0038) and of its ligand, CXCL10 (p=0,0169), compared to patients who did not relapse. Conclusions Our study suggests that the CXCR3/CXCL10 axis may be involved in the CNS relapse of high-risk ALL in children: high expression of CXCR3 on marrow blasts plus high levels of CXCL10 in the CNS was associated with leukemic CNS relapse. Disclosures No relevant conflicts of interest to declare.

Liposomal Cytarabine (DepoCyte®) for the Prophylaxis and Treatment of Central Nervous System Involvement In Adult Acute Lymphoblastic Leukemia (ALL) - A Retrospective Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2122-2122
Author(s):  
Beata Piatkowska-Jakubas ◽  
Wojciech Jurczak ◽  
Sebastian Giebel ◽  
Aleksandra Holowiecka-Goral ◽  
Maria Adamczyk-Cioch ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Systemic Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Concomitant Administration ◽  
Liposomal Cytarabine ◽  
Female Ratio ◽  
Cns Relapse ◽  
Male Female Ratio

Abstract Abstract 2122 Background: Central nervous system involvement in Acute Lymphoblastic Leukemia can be either primary, present at diagnosis or associated with relapse of the disease. Prevention and treatment of CNS relapse is an essential component of all ALL chemotherapy regimens. Liposomal cytarabine (DepoCyte) is a sustained release formulation of Ara-C with a homogeneous distribution throughout the neuroaxis and a prolonged half-life maintaining cytotoxic concentrations in the CSF for more than 14 days. DepoCyte obtained superior response rates, improved patient quality of life and improved the time to neurological progression compared to standard cytarabine in a randomized clinical trial (Glantz et al 1999). Materials and Methods: A retrospective analysis was carried out to evaluate feasibility, safety and efficacy of DepoCyte in the prophylaxis and treatment of ALL patients. 45 patients who received 50mg liposomal cytarabine either as a prophylaxis (N=24) or treatment (N=21) between March 2006 – December 2009 in 4 centers in Poland were included in the analysis. Baseline characteristics of patients who completed CNS prophylaxis with DepoCyte: median age 34 (range: 18–67 years), male/female ratio 16/8, B-cell ALL (n=17), T-cell ALL (n=4), Ph-positive ALL (n=3). In the treatment group median age was 35 (range 18–60), male/female ratio 12/9, B-cell ALL (n=15), T-cell ALL (n=3) and Ph-positive ALL (n=3). Results: In the prophylaxis group the average number of DepoCyte administrations was 2.6 (range 2–4). Oral or IV Dexamethasone for 5 days was given to all patients to prevent symptoms of arachnoiditis. With a median follow-up of 12 months (range: 3–27) only 1 pt developed combined systemic and CNS relapse. 25% of patients (6/24) experienced mild and transitory adverse events: headache (n=3), brain edema during methotrexate-containing consolidation (n=1) and post-puncture syndrome (n=2). In the treatment group 8 pts were in first isolated CNS relapse and 13 pts were in combined CNS and systemic relapse. All patients had neurological symptoms and blast cells identified in the cerebrospinal fluid with average cellularity 713/μL (range 20–2500/μL). In 2 patients CNS disease was confirmed by computed tomography. DepoCyte was administered intrathecally together with systemic chemotherapy in 18 patients. The treatment was planned to avoid concomitant administration of DepoCyte and other cytotoxic agents that cross the BBB. All patients received concurrent dexamethasone for prophylaxis of arachnoiditis. Neurological and cytological responses were obtained in all 21 pts (16 CRs and 5 PRs). No serious adverse events with DepoCyte were reported. Mild headache was the most commonly reported toxicity (10/21pts, 47.6%). 2 out of 21 (9.5%) heavily pretreated patients developed transient sacral radiculopathy. Conclusions: 1) Implementation of liposomal cytarabine as IT prophylaxis in ALL patients reduces the total number of IT injections, is feasible and effective and has a favorable tolerance profile. 2) DepoCyte used for the treatment of leukaemic meningitis with concurrent systemic chemotherapy is a highly effective and feasible treatment in isolated and combined CNS relapse in ALL. 3) DepoCyte is generally well tolerated when concurrent dexamethasone is administered to alleviate symptoms of arachnoiditis and concomitant administration of agents that cross the BBB is avoided. Reference: Glantz M et al. Randomized trial of a slow release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999; 17: 3110-17. Disclosures: No relevant conflicts of interest to declare.

Central Nervous System Relapse In Adults With Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3311-3311
Author(s):  
Amir Hamdi ◽  
Raya Mawad ◽  
Antonio Di Stasi ◽  
Roland Bassett ◽  
Roberto Ferro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Cns Involvement ◽  
Hematopoietic Stem ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
History Of ◽  
First Relapse

Abstract Introduction Central nervous system (CNS) recurrence after allogeneic hematopoietic stem cell transplantation (HSCT) confers a poor prognosis in adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence after HSCT remains a therapeutic challenge, and criteria for post-HSCT CNS prophylaxis have not been addressed. Our goal was to investigate the post-HSCT outcome of ALL patients and identify patient groups who may benefit from post-HSCT CNS prophylaxis. Methods In this two-center retrospective study, we studied all adult (age≥18) ALL patients who underwent HSCT at MD Anderson Cancer Center or Fred Hutchinson Cancer Research Center between 1997 and 2011. We included all adult ALL patients who were transplanted in the first or second complete remission (CR) and who received any prophylactic or therapeutic CNS therapy before HSCT. We assessed the cumulative incidence of systemic and CNS relapses in a competing risks framework with a competing risk of non-relapse death. Since data from second and subsequent relapses were not available, patients whose first relapse did not include CNS involvement were censored at the time of relapse. To analyze the association between post-HSCT CNS prophylactic therapy and CNS relapse, we used a landmark analysis, including only patients who had not relapsed or died by 3 months post HSCT. Results We included 415 adult ALL patients (239 in CR1 and 176 in CR2) who were transplanted with a myeloablative total body irradiation based (MA-TBI, n=252), myeloablative non-TBI based (MA-nonTBI, n= 130), or reduced intensity conditioning regimen (RIC, n=33). Median age at HSCT was 37 years (range 18-70; 59% male). Sixty seven patients (16%) had a history of pre-HSCT CNS involvement either at diagnosis or at time of first relapse, while 339 patients (81%) had no CNS disease at any time before HSCT. Overall 175 patients (42%) received CNS prophylaxis after HSCT. CNS prophylaxis included intrathecal methotrexate, cytarabine, or both agents. Two patients received prophylactic cerebrospinal radiotherapy. The median follow-up for the 189 surviving patients was 4.2 years. Sixteen patients (3.8% of all patients, 13.2% of all relapses) developed CNS relapse (11 isolated and 5 combined with marrow relapse) at a median of 231 days (range 38-1397) after HSCT. Seven of these patients had pre-HSCT CNS disease. The 4-year cumulative incidence of relapse after HSCT among all patients was 31.7% and 28.2% for patients with and without CNS prophylaxis after HSCT, respectively (P=0.51). The 4-year cumulative incidence of CNS relapse was 6% and 2.6% for patients with and without CNS prophylaxis after HSCT, respectively (P=0.16) (Figure 1). When the analysis was limited to the patients without prior CNS involvement, there was still no benefit to post-HSCT CNS prophylaxis (P=0.63). Patients with a prior history of CNS involvement with leukemia had a significantly higher rate for CNS relapse, 11.6% vs. 2.7% (P=0.003) (Figure 2). The 4-year rate of CNS relapse was not impacted by intensity of the HSCT conditioning regimen and was 3%, 4%, and 6.5% for RIC, MA-TBI, and MA-nonTBI, respectively. Conclusion CNS relapse is an uncommon event following HSCT for ALL in CR1 or CR2. Furthermore, neither the intensity of the HSCT conditioning regimen nor the routine use of post-HSCT CNS prophylaxis made a significant difference in the rate of post-HSCT CNS relapse in patients who had received CNS prophylaxis prior to HSCT. Not surprisingly, patients with a pre-HSCT history of CNS involvement had a significantly higher risk of CNS relapse after HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Concurrent hypopituitarism and leukemic retinopathy in a child with B-precursor acute lymphoblastic leukemia and isolated central nervous system relapse

2016 ◽  
Vol 23 (4) ◽  
pp. 431
Author(s):  
K.H. Wu ◽  
H.P. Wu ◽  
H.J. Lin ◽  
C.H. Wang ◽  
H.Y. Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Systemic Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
Central Nervous System Relapse ◽  
Cns Involvement ◽  
Lower Extremity Weakness ◽  
Cns Relapse

Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse. Concurrent hypopituitarism and leukemic retinopathy were also found. After receiving craniospinal radiotherapy and systemic chemotherapy, her retinopathy and vision improved. She is now in complete remission, and she is still on chemotherapy according to the guideline from the Pediatric Oncology Group. Although rare, hypopituitarism and leukemic retinopathy should be taken into consideration in patients with cns involvement by leukemia.

scholarly journals Successful Bosutinib Experience in an Elderly Acute Lymphoblastic Leukemia Patient with Suspected Central Nervous System Involvement Transformed from Chronic Myeloid Leukemia

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Erden Atilla ◽  
Pinar Ataca ◽  
Elif Ozyurek ◽  
Ilhan Erden ◽  
Gunhan Gurman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Limited Data ◽  
Cns Involvement ◽  
Blast Phase ◽  
The Central Nervous System

Managing the blast phase in chronic myeloid leukemia (CML) is challenging because limited data are available for elderly patients. The involvement of the central nervous system (CNS) increases the risk of a poor prognosis. Here, we present an elderly blast phase CML patient with suspected CNS involvement who was successfully treated with bosutinib.

Incidence and Outcome In Adults With Acute Lymphoblastic Leukemia With Primary Central Nervous System Involvement

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2639-2639
Author(s):  
Muhamed Baljevic ◽  
Hagop M Kantarjian ◽  
Deborah Thomas ◽  
Michael Rytting ◽  
Jyothsna Dasarathula ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Cns Involvement ◽  
Cytologic Examination ◽  
Cell Counts ◽  
Remission Duration

Abstract Background Presence of primary central nervous system (pCNS) involvement at the time of diagnosis of acute lymphoblastic leukemia (ALL) in adults is a poor prognostic feature. Few reports have systematically analyzed the outcomes of adult patients (pts) diagnosed with CNS involvement at diagnosis of ALL. This report provides analysis of single institution experience outcomes in adult pts diagnosed and treated for ALL with pCNS involvement with the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (HCVAD) or augmented Berlin-Frankfurt-Munster (AUG-BFM) based induction regimens, with or without the frontline use of Rituximab and tyrosine kinase inhibitors (TKIs). Methods The records of 623 consecutive pts with newly diagnosed ALL treated at the M. D. Anderson Cancer Center between January 2001 and June 2013 were reviewed. Those who had CNS involvement at diagnosis were treated with intrathecal (IT) chemotherapy twice weekly until at least 2 consecutive cerebrospinal fluid (CSF) cell counts normalized and cytologic examination was negative for evidence of malignant cells. IT therapy was subsequently administered weekly for at least 6-8 weeks, then according to the prophylactic schedule (2 intrathecals per course) for the remaining courses of intensive chemotherapy. Results A total of 68 (11%) pts had pCNS involvement by analysis of CSF; 5 (7%) had additional brain, leptomeningeal, base of skull or spine evidence of involvement. They were treated with either HCVAD (n=52) or AUG-BFM (n=16). HCVAD with Rituximab was used in 22 (32%), and HCVAD with Dasatinib or Ponatinib in 17 (25%). Median age at diagnosis was 38 (range 13-80); 45 (66%) were male; median white blood cell count 9.9 (vs. 6.7 for those with no pCNS involvement; p=0.007); peripheral blood blast 46% (vs. 18; p=0.0008); lactate dehydrogenase 1266 (vs. 1013; p=0.03); albumin 3.3 (vs. 3.55; p=0.03); platelets 54; hemoglobin 9.3; bone marrow blast 83%. Philadelphia chromosome (Ph+) was seen in 18 (26%) vs. 140 (25%) of pts with no pCNS involvement. Among pts with pCNS, 46% expressed CD20 vs. 47% of pts with no pCNS involvement. Complete response (CR) was achieved in 61 (90%) pts compared to 513 (92%) among those with no pCNS involvement (p=0.465). Of those with CNS disease who achieved CR, 21 (34%) had a relapse, compared to 138 (27%) among those with no CNS involvement. Median complete remission duration has not been reached; Kaplan-Meier estimates for remission duration at 18 months are 66% vs. 81% for pts with with or without pCNS, respectively (p=0.147). Overall, 6 (10%) of pts with pCNS disease who had a recurrence had an isolated CNS relapse; 3 (50%) of them had a baseline Ph+. They were treated with combination therapy including HCVAD and IT cytarabine and/or methotrexate with or without craniospinal radiation and allogeneic stem cell transplantation. Five (24%) reached the second CR. The median overall survival (OS) was 28 mo for pts with pCNS involvement vs. 86 mo for those without CNS involvement at presentation (p=0.036). Of those who were evaluable in the CNS cohort, 48 (74%) pts were alive at 1 year, and 24 (41%) were alive at 4 years. Conclusion The incidence of pCNS involvement in adults with ALL has remained virtually the same over the last 20 years; 10% for HCVAD treated cohort (Cortes et al. Blood. 1995). Despite effective and wider therapeutic arsenal for ALL including Rituximab and advanced generation TKIs since year 2000, adults with ALL who present with pCNS involvement have an inferior outcome, with shorter median OS compared to pts who do not present with pCNS disease. However, pCNS is still compatible with cure if properly treated. Disclosures: No relevant conflicts of interest to declare.

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