CENTRAL NERVOUS SYSTEM RADIOTHERAPY IN ACUTE LEUKEMIA

From Dec. 1976 through June 1986, 474 patients with acute leukemia were treated with central nervous system (CNS) irradiation for the purpose of preventing relapse of CNS leukemia. Of the whole series, whole cranial irradiation at a dosage of 24 Gy and 4-5 intrathecal instillations of methotrexate (MTX) were given in 149 patients, simple intrathecal instillation of MTX in 44 patients and high dose intravenous MTX in 5 patients; the CNS relapse rates were 4.0%, 20.5% and 40.0% respectively. It was proved by our experience that whole cranial irradiation plus intrathecal MTX is the best approach to prevention of CNS leukemia relapses.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Primary isolated central nervous system acute lymphoblastic leukemia with BCR-ABL1 rearrangement:A case report

BACKGROUND BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system(CNS)leukemia.CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration.It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement.CASE SUMMARY We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis,with no involvement in peripheral blood or bone marrow.Identification of abnormal phenotypes of blast cells,and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia.The patient received a combination of intrathecal therapy and high-dose chemotherapy.But the benefits of the treatments were short-lived and she experienced recurrence.CONCLUSION Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy.New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.

Central nervous system recurrence in a patient treated for acute promyelocytic leukemia,resulting in sideroblastic anemia:A case report

BACKGROUND Previous cases that have been stated in this article have displayed that around 1%to 7%of patients that have been treated with chemotherapy for acute promyelocytic leukemia developed myelodysplastic syndrome or acute myeloid leukemia.One can see that’s why this case presentation of a 60-year-old man that had a good response to acute promyelocytic leukemia treatment,that later presented with a central nervous system recurrence of acute promyelocytic leukemia and acquired sideroblastic anemia(a form of myelodysplasia)from treatment is a unique case report.CASE SUMMARY The presence of central nervous system relapse in acute promyelocytic leukemia patients is very unlikely compared to recurring mainly in the bone marrow.It is also uncommon to be diagnosed with sideroblastic anemia(form of myelodysplastic syndrome)as a result from treatment for acute promyelocytic leukemia.This case report highlights the detection,treatment/maintenance with idarubicin,all-trans-retinoic-acid,arsenic trioxide,methotrexate,6-mercaptopurine,and ommaya reservoir intrathecal methotrexate administration in a patient that had central nervous system relapse of acute promyelocytic leukemia and acquired sideroblastic anemia.CONCLUSION In essence,first time relapse concerning the central nervous system in treated acute promyelocytic leukemia patients who had a good response to therapy is very uncommon.The acquirement of a myelodysplastic syndrome such as ringed sideroblastic anemia is also rare regarding this patient population.Although such cases are infrequent,this case report represents a unique insight of the detection,treatment,and maintenance of a 60-year-old man diagnosed with acute promyelocytic leukemia,resulting in the acquirement of sideroblastic anemia and central nervous system relapse.

A novel mouse model of adult T-cell leukemia cell invasion into the spinal cord

Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc~ (scid) Il2 rg ^(tm1Wjl)/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly(I.M.) at 5 weeks of age, 8(80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously(S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.

Predictive role of cerebrospinal fluid hydrogen sulfide in central nervous system leukemia

Background Central nervous system leukemia （CNSL） is an important relapse in children with acute lymphoblastic leukemia （ALL）. We investigated the possible role of endogenous hydrogen sulfide （H2S） of cerebrospinal fluid （CSF） in predicting CNSL. Methods From August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group （7 cases）, a leukemia group （307 cases）, a non-leukemia group （26 cases） and a healthy group （40 children）. CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H2S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction （RT-PCR）, and H2S levels in serum were also measured. The receiver operating characteristic （ROC） curve and area under curve （AUC） were used to assess the predictive diagnosis role of CSF H2S in children with ALL and CNSL. Results The serum H2S contents of the CNSL and leukemia groups were （96.98±15.77） pmol/L and （93.35±17.16） μmol/L respectively, much higher than those of healthy, （44.29±2.15） pmol/L, and non-leukemia, （46.32±6.54） μmol/L, groups （P 〈0.01）. Compared with the leukemia group, CSF H2S content of the CNSL group was significantly high （P 〈0.01）. Meanwhile, in contrast to the non-leukemia group, CSF H2S contents of the CNSL and leukemia groups were both significantly increased （P 〈0.01）. In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 （95% CI： 0.857-1.000）, and the optimum cut-off value of CSF H2S was 12.08μmol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively. Conclusions CSF H2S contents were significantly increased in children with CNSL. After treatment, H2S contents were decreased subsequently. Therefore, we speculated that H2S levels of CSF would predict CNSL in ALL children.

整合素α6靶向自组装促凋亡纳米多肽对中枢神经系统急性淋巴细胞白血病的靶向治疗

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.

Diagnosis and management of adult central nervous system leukemia

Central nervous system leukemia(CNSL)is a prominent infiltration reason for therapy failing in acute leukemia.Recurrence rates and the prognosis have alleviated with current prophylactic regimens.However,the accurate stratification of relapse risk and treatment regimens for relapsed or refractory patients remain clinical challenges yet to be solved.Recently,with hematopoietic stem cell transplantation(HSCT)and chimeric antigen receptor-T(CAR-T)cellular therapy showing encouraging effects in some CNSL patients,advances in treating CNSL have already been reported.The development of molecular targeted agents as well as antibody-based drugs will provide patients with more personalized treatment.This article summarized recent research developments about risk factors,diagnosis,prevention,and treatment in adults with CNSL.

儿童急性淋巴细胞性白血病并发中枢神经系统白血病的临床治疗研究

目的 :探讨儿童中枢神经系统白血病复发再治疗的安全有效方法。方法 :应用国产 60Co ,对 2 7例曾接受全颅、全脊髓放射治疗和 (或 )鞘内注射后CNSL复发的儿童急性淋巴细胞性白血病进行全颅、全脊髓间歇性放射治疗 ,并联合鞘内注射。治疗方案为 :全颅 1 5Gy/次 +全脊髓 0 75Gy/次 ,1次 /d照射 3d。第 1天鞘内注射甲氨蝶呤 (MTX ) 8～ 12mg/m2 ,阿糖胞苷 (Ara C) 2 5mg/m2 ,地塞米松 (DXM ) 2～ 5mg/次 ,以后每 8周全颅1 5Gy +全脊髓 0 75Gy照射 1次 ,当天鞘内注射 ,用药剂量同前。总疗程为 2年2个月。结果 :2 7例患者中 ,3年内死于骨髓复发 4例、CNSL复发 2例 ;3～ 5年内死于骨髓复发 5例、CNSL复发 8例 ,3、5年生存率分别为 77 8% (2 1/2 7)、2 5 9%(7/2 7)。间歇性放射治疗过程中未发现明显急性毒副反应。随访期间发现 5例记忆力差、注意力不易集中现象。结论 :间歇性放射治疗联合鞘内注药对于曾接受全中枢神经系统放射治疗和 (或 )鞘内注射后CNSL复发的儿童急性淋巴细胞性白血病安全而有效。

Primary mucosa-associated lymphoid tissue lymphoma in the midbrain:A case report

BACKGROUND Primary non-dural central nervous system mucosa-associated lymphoid tissue(MALT)lymphoma is a rare indolent B-cell lymphoma,with only a few reported cases worldwide.CASE SUMMARY A 33-year-old man presented with a 5-mo history of left blepharoptosis and a 4-mo history of right limb numbness and weakness.Magnetic resonance imaging showed a significantly enhanced mass in the left midbrain.Subsequent positron emission tomography revealed that the lesion had increased glucose uptake.A stereotactic robotic biopsy supported a diagnosis of MALT lymphoma.Then he was treated with radiation therapy(30Gy/15F),which resulted in complete remission.We also review the literature on brain parenchymal-based MALT lymphoma,including the clinical presentation,treatment options,and outcomes.CONCLUSION Although there is no consensus on the optimal treatment for this rare disease,patients can respond well when treated with radiotherapy alone.

小儿中枢神经系统白血病间歇性放射治疗的临床研究(附13例病例报道)

目的以间歇性放射治疗＋鞘内注射方法治疗曾接受全颅、全脊髓放射治疗和（或）鞘内注射后中枢神经系统白血病（ＣＮＳＬ）复发的急性淋巴细胞性白血病（ＡＬＬ）患儿，以便建立一种在达到治疗目的的前提下尽量减少第２次放射治疗引起的晚期并发症的放射治疗方案。方法应用国产８ＭＶ直线加速器，选择１３例曾接受全颅、全脊髓放射治疗和（或）鞘内注射后ＣＮＳＬ复发的急性淋巴细胞性白血病患儿进行全颅、全脊髓间歇性放射治疗，并联合鞘内注射。治疗方案为：全颅１５０ｃＧｙ／次＋全脊髓７５ｃＧｙ／次，每日１次照射３天。第１天鞘内注射甲氨喋呤（ＭＴＸ）８～１２ｍｇ／ｍ２，阿糖胞苷（ＡｒａＣ）２５ｍｇ／ｍ２，地塞米松（ＤＸＭ）２～５ｍｇ／次，以后每８周全颅１５０ｃＧｙ＋全脊髓７５ｃＧｙ照射１次，当天鞘内注射，用药剂量同前。总疗程为２年２个月。结果９例患儿随访５年以上，４例随访３年以上。１３例患儿中２例分别于放射治疗结束后５个月、１２个月因骨髓复发死亡。生存者均未再发生ＣＮＳＬ。结论间歇性放射治疗过程中未发现明显急性副反应。随访期间发现２例记忆力差、注意力不易集中现象。间歇性放射治疗对于曾接受全中枢神经系统放射治疗和（或）鞘内注射后ＣＮＳＬ复发的急?

小儿急性淋巴细胞白血病最新治疗方案介绍

20世纪60～80年代，小儿急性淋巴细胞白血病（ALL）治疗方案中包含较多传统的中枢神经系统向血病（CNSL）治疗方法，如鞘内注射（IT）、化疗、头颅放疗及大剂量甲氨蝶呤（MTX）等。放射治疗有许多伴随问题，如第二肿瘤、生长发育障碍、内分泌异常等，放疗剂量越大、年龄越小（〈5岁），其发生率越高。因此，头颅放疗的适应证越来越严格，剂量也有所减低，头颅放疗已不用于标危患儿。