Background

Acute lymphoblastic leukemia (ALL) is a leukemia derived from lymphoblasts, primitive progenitor cells originating in the bone marrow. It is most common type of leukemia in children. Patients present with flu-like symptoms, joint pain, and bleeding tendencies with easy bruising. In spite of the ominous diagnosis of leukemia, ALL remains one of the great success stories of oncology. Improvements in chemotherapy and prophylactic treatment as well as insights into the molecular mechanisms have contributed to the advances. In addition, bone marrow transplants provide another treatment option.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Acute lymphocytic leukemia
INCIDENCE	80-85% of cases of childhood leukemias
AGE RANGE-MEDIAN	70% occur <17 years of age
SEX (M:F)	1.4:1
EPIDEMIOLOGIC ASSOCIATIONS
Down syndrome	Occasional cases of ALL with azurophilic granules

 

DISEASE ASSOCIATIONS

CHARACTERIZATION

Langerhans cell histiocytosis in a child while in remission for acute lymphocytic leukemia Lenore R. Chiles, MD Mary M. Christian, MD Danny K. McCoy, MD Hal K. Hawkins Angela H. Yen, MD Sharon S. Raimer, MD Galveston, Texas

J Am Acad Dermatol 2001;45:S233-4 Abstract quote The occurrence of Langerhans cell histiocytosis (LCH) and malignancy in the same patient is rare. When LCH occurs concomitantly with acute leukemia, distinct temporal patterns often exist; acute myelogenous leukemia (AML) typically succeeds LCH, whereas acute lymphocytic leukemia (ALL) usually precedes it. We report a case of LCH developing in a child while in remission for ALL. Unique features of this case include the disseminated nature of the LCH and the death of the patient from LCH rather than ALL.

 

PATHOGENESIS	CHARACTERIZATION
CHROMOSOMAL STRUCTURAL CHANGES
Philadelphia chromosome (Ph) t(9;22)
t(1;19)(q23;p13)
Reciprocal translocations involving chromosome 8q24
t(11;14)(p13;q11)
t(4;11)(p21;q23)
t(5;14) translocation	Associated with ALL with eosinophilia
Absence of Somatic Hypermutation of Immunoglobulin Heavy Chain Variable Region Genes in Precursor B-Lymphoblastic Lymphoma A Study of Four Cases in Childhood and Adolescence Hiroshi Hojo, MD, Yoshikazu Sasaki, Naoya Nakamura, MD, and Masafumi Abe, MD	Am J Clin Pathol 2001;116:673-682 Abstract quote Somatic mutation (SM) analysis provides a useful tool for understanding the suitable stage of differen-tiation of normal and neoplastic B cells. B-cell precursor neoplasms are considered to be somatically premutational. However, no reports have been made on the sequence analysis of SM in rearranged immunoglobulin heavy chain variable region (VH) genes in precursor B-lymphoblastic lymphoma (PB-LBL); as for B-cell acute lymphoblastic leukemia (B-ALL), the variable frequency of SM of the VH genes has been described. To better distinguish PB-LBL from B-ALL based on the stage at which differentiation occurs, we analyzed the SM of the VH genes in 4 children and adolescents with PB-LBL. In all 4 cases, there was no SM in complementarity-determining regions 1, 2 and 3 and in framework regions 2 and 3 of the VH genes, except for 1 mutation in 1 of 2 polymerase chain reaction products from 1 patient. Our data showed the absence of SM of lymphoma cells in PB-LBL, in addition to the developmentally regulated rearrangement of VH genes at the stage of B-cell precursor cells. The lack of mutation in VH gene sequences suggests that SM may differ between PB-LBL and B-ALL.

 

CLINICAL VARIANTS	CHARACTERIZATION
GYNECOLOGICAL
Precursor T-cell acute lymphoblastic leukemia/lymphoma involving the uterine cervix, myometrium, endometrium, and appendix. Lyman MD, Neuhauser TS. Department of Pathology, Wilford Hall Medical Center, San Antonio, TX.	Ann Diagn Pathol 2002 Apr;6(2):125-8 Abstract quote This report presents a case of precursor T-cell acute lymphoblastic leukemia/lymphoma (ALL) involving the uterine cervix, myometrium, endometrium, and appendix. The patient was a 38-year-old woman with a history of ALL who had been in remission for 4 years following chemotherapy. The malignant lymphoid infiltrate was characterized by blasts, showing scant cytoplasm, irregular hyperchromatic nuclei, and occasional prominent nucleoli. They were immunoreactive for CD45RB, CD3, CD43, CD34, and focally for TdT. Curiously, the blasts replaced the endometrial stroma and spared the associated epithelium. The patient was again treated with chemotherapy but her disease did not respond. She succumbed to her disease approximately 10 months after her initial evaluation for symptoms related to ALL relapse. Precursor T-cell ALL most commonly presents as a mediastinal mass in adolescent males. Although any organ may be affected, involvement of the female reproductive organs is rare. This case shows some of the varied manifestations of precursor T-cell ALL and highlights the necessity of considering the female reproductive tract as a possible location of relapsing disease.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
French-American-British (FAB) Cooperative Group Classification	Defined the cytologic features of ALL based upon Romanowsky stained bone marrow smears In general, concentrates upon four cytologic criteria: Nuclear:cytoplasmic ratio Nucleoli Nuclear membrane irregularity Lymphoblast size
L1	80-88% of cases Small cells usually twice the size of normal small lymphocytes, sparse cytoplasm, high N/C ratio Round nuclei with slight nuclear indentations and convoluted nuclear outlines
L2	8-18% of cases Larger than L1 with considerable heterogeneity with nuclear irregularity Lower N/C ratio compared to L1 Nucleoli prominent varying from 1-4 Cytoplasm variably basophilic with occasional vacuoles
L3	1-3% fo cases Similar features to small noncleaved cell lymphoma of Burkitt and non-Burkitt type Round to oval nuclei with nuclear irregularities Stippled and homogeneous chromatin 2-4 nucleoli Deeply basophilic abundant cytoplasm with cytoplasmic vacuoles-oil-red-O positive
VARIANTS OF ALL
ALL with cytoplasmic granules	4.5-7% of cases Azurophilic granules staining weakly pink or orange Usually B-cell precursor phenotype Has been associated with Down syndrome May be associated with poor prognosis in ALL-L2 cases
Aplastic presentation of ALL	Rare cases of ALL presenting with pancytopenia and hypoplastic bone marrow This is followed within a few weeks by overt leukemia within a few weeks or months
Bone marrow necrosis	May present with extensive bone marrow necrosis Overt leukemia may be present with repeat bone marrow biopsy
ALL with eosinophilia	Has been reported with L1 and L2 No correlation with immunophenotype Associated with t(5;14) translocation
Hand-mirror cells	Blasts have a a cytoplasmic projection resembling hand-mirrors No association with immunophenotype, cytogenetics, or prognosis
T-cell ALL	15% of ALL Older median age Males 50% incidence of mediastinal mass High blood leukocyte counts Chromosomal rearrangements involving 14q11 Earlier relapse than non-Tcell ALL High incidence of CNS relapse Shorter survival than non-T-cell ALL FAB class L1 and L2 TdT positive with T cell lineage antigens
Indolent T-Lymphoblastic Proliferation Report of a Case With an 11-Year History and Association With Myasthenia Gravis	Am J Surg Pathol 2001;25:411-415 In the present case, we report on an indolent T-lymphoblastic proliferation involving the oropharynx in a patient with myasthenia gravis with multiple local recurrences over an 11-year period without evidence of systemic dissemination. The T-lymphoblasts were consistently positive for terminal deoxynucleotidyl transferase (TdT), CD1, CD3, CD4, and CD8, corresponding to an intermediate thymocyte stage of differentiation. No cytokeratin-positive thymic epithelial cells were identified, ruling out an ectopic thymus or thymoma. T-receptor gene rearrangement studies by Southern blot revealed no monoclonal CT-beta rearrangement. Conclusions: Indolent T-lymphoblastic proliferations of undetermined clonality may rarely occur; predilection for involvement of oropharynx and possible association with myasthenia gravis are suggested.
Precursor T-Cell Acute Lymphoblastic Leukemia in Adults Age-Related Immunophenotypic, Cytogenetic, and Molecular Subsets Mihaela Onciu, MD, Raymond Lai, MD, PhD, Francisco Vega, MD, Carlos Bueso-Ramos, MD, PhD, and L. Jeffrey Medeiros, MD	Am J Clin Pathol 2002;117:252-258 Abstract quote We analyzed the clinicopathologic and molecular findings in 26 adults (age 16-72 years) with T-cell acute lymphoblastic leukemia (T-ALL) and observed features that correlated with age. Patients older than 60 years (n = 5) had a low frequency of hepatosplenomegaly (0 [0%]), anterior mediastinal mass (1 [20%]), and lymphadenopathy (2 [40%]), and completely responded to chemotherapy (4 of 4). The T-ALL in this group commonly expressed myeloid antigens (4 [80%]), had lineage-inappropriate gene rearrangements (2/3 [67%]) and chromosome 2 deletion (3/4 [75%]), and exclusively used the VIII or VIV families of the T-cell receptor (TCR) gamma gene. In comparison, patients 16 to 60 years old (n = 21) more commonly had an anterior mediastinal mass (8 [38%]), hepatosplen-omegaly (10 [48%]), and lymphadenopathy (16 [76%]). The tumors in these patients commonly used the TCR gamma gene VI or VII families (17/25 total rearrangements [68%]). Myeloid antigen expression (5 [24%]) and lineage inappropriate gene rearrangements (4/15 [27%]) were uncommon. Within this group, CD1a expression correlated with age 28 to 60 years. These results illustrate considerable age-related heterogeneity in adult T-ALL, which may reflect differences in tumor cell maturation.
B-CELL ALL	1-3% of cases Older median age High incidence of abdominal mass-usually ileocecal High incidence of CNS disease Chromosomal translocations involving 8q24 Poor reponse to therapy Early relapse Surface Immunoglobulins and pan-B cell antigens
Mature B-cell acute lymphoblastic leukemia with t(9;11) translocation: a distinct subset of B-cell acute lymphoblastic leukemia. Tsao L, Draoua HY, Osunkwo I, Nandula SV, Murty VV, Mansukhani M, Bhagat G, Alobeid B. Department of Pathology, Columbia University, New York, NY 10032, USA.	Mod Pathol. 2004 Jul;17(7):832-9. Abstract quote   Mature B-cell acute lymphoblastic leukemia (ALL) is typically associated with the FAB-L3 morphology and rearrangement of the MYC gene, features characteristic of the leukemic phase of Burkitt's lymphoma. However, the term 'mature' has also been used to describe other rare cases of B-ALL with light-chain surface immunoglobulin expression. In contrast, infantile B-cell ALL is generally characterized by rearrangement of the MLL gene, an immature pro-B-cell phenotype, and CD10 negativity. We describe two unusual cases of infantile B-ALL with non-L3 morphology, expressing a mature B-cell phenotype (lambda sIg+, CD19+, CD10-, TdT-, and CD34-), and showing MLL rearrangement without MYC rearrangement at presentation. Both infants relapsed after months of morphologic and genetic remission. At relapse, the t(9;11) translocation was detected in both cases by spectral karyotyping. After the initial relapse, both cases followed a rapid and aggressive course. Literature search identified few similar cases, all expressed lambda surface immunoglobulin and showed MLL rearrangement (majority with the t(9;11) translocation). These cases show that B-ALL with MLL rearrangement, especially the t(9;11) translocation, can express a 'mature' B-cell phenotype and may represent a distinct subset. Identification of additional cases will further clarify the significance of MLL rearrangements in mature B-ALL.
PRECURSOR B LYMPHOBLASTIC LEUKEMIA
Precursor B Lymphoblastic Leukemia With Surface Light Chain Immunoglobulin Restriction A Report of 15 Patients Rina Kansal, MD, etal.	Am J Clin Pathol 2004;121:512-525 Abstract quote We describe 15 patients (9 children) with precursor B-cell (pB) acute lymphoblastic leukemia (ALL) with surface immunoglobulin (sIg) light chain restriction revealed by flow cytometric immunophenotyping (FCI). The same sIg+ immunophenotype was present at diagnosis and in 3 relapses in 1 patient. In 15 patients, blasts were CD19+CD10+ (bright coexpression) in 14, CD34+ in 12, surface k+ in 12, surface l+ in 3; in 8 of 8, terminal deoxyribonucleotidyl transferase (TdT)+; and in 4, surface IgD+ in 2 and surface IgM+ in 1. The 3 CD34– cases included 1 TdT+ case, 1 with t(1;19)(q23;p13), and 1 infant with 70% marrow blasts. One adult had CD10–CD19+CD20–CD22+CD34+ TdT+sIg+ blasts with t(2;11)(p21;q23). Blasts were L1 or L2 in all cases (French-American-British classification). Karyotypic analysis in 12 of 12 analyzable cases was negative for 8q24 (myc) translocation. Karyotypic abnormalities, confirmed by fluorescence in situ hybridization in 6 cases, included hyperdiploidy, t(1;19)(q23;p13), t(12;21)(p13;q22), t(9;22)(q34;q11), t(2;11)(p21;q23), and trisomy 12. The sIg light chain restriction in pB ALL might be present in neoplasms arising from the early, intermediate, and late stages of precursor B-cell maturation; sIg light chain restriction revealed by FCI does not necessarily indicate a mature B-cell phenotype, further emphasizing the importance of a multidisciplinary approach to diagnosing B-lymphoid neoplasms.
Asynchronous	>50% of B-cell precursor cases exhibit expressions of combinations of early and late antigens not present on normal lymphoid cells
Mixed phenotype	15-20% of ALL have blasts exhibiting one or more myeloid antigens More common in adults
Bilineal	Two distinct leukemia cells lines, one exhibiting lymphoid and myeloid differentiation In adults with ALL, myeloid antigen-positive blasts is indicator of poor prognosis

 

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
L1 and L2	Positive for PAS, acid phosphatase, and +/- for nonspecific esterase and methyl green pyronine
L3	Positive for Oil-red-O in cytoplasmic vacuoles and methyl green pyronine Negative for PAS, acid phosphatease
TdT (Terminal deoxynucleotidyl-transferase)	DNA polymerase found in the nuclei of cortical lymphocytes >90% of T-cell and B-cell precursor ALL are positive
Nonpositive Terminal Deoxynucleotidyl Transferase in Pediatric Precursor B-Lymphoblastic Leukemia Lanting Liu, MD, etal.	Am J Clin Pathol 2004;121:810-815 Abstract quote Terminal deoxynucleotidyl transferase (TdT) is a unique intranuclear DNA polymerase that catalyzes the template-independent addition of deoxynucleotides to the 3'-hydroxyl terminus of oligonucleotide primers. The expression of TdT is restricted to lymphoid precursors. It is a useful marker in distinguishing acute lymphoblastic leukemia (ALL) from mature lymphoid neoplasms. Although TdT– T-cell ALL has been reported in the literature rarely, the frequency and significance of TdT-nonpositive (TdTnp) B-cell ALL have not been examined extensively. We reviewed the immunophenotypes of 186 new cases of pediatric B-cell ALL and found 5 TdTnp cases (2.7%). They showed significantly higher frequencies of a WBC count of more than 50,000/µL (>50.0 × 109/L), CD10–, CD34–, and MLL gene rearrangement compared with those in TdT+ cases (3/5 [60%] vs 27/181 [14.9%], P = .03; 3/5 [60%] vs 11/181 [6.1%], P = .003; 4/5 [80%] vs 24/179 [13.4%], P = .002; 3/5 [60%] vs 9/181 [5.0%], P = .0019; respectively). These results indicate that nonpositive TdT does not rule out a diagnosis of ALL and suggest that TdTnp B-cell ALL might be associated with CD10– and CD34– disease, a high WBC count, and MLL gene rearrangement.
CD179
Diagnostic importance of CD179a/b as markers of precursor B-cell lymphoblastic lymphoma. Kiyokawa N, Sekino T, Matsui T, Takenouchi H, Mimori K, Tang WR, Matsui J, Taguchi T, Katagiri YU, Okita H, Matsuo Y, Karasuyama H, Fujimoto J. Department of Developmental Biology, National Research Institute for Child Health and Development, Japan.	Mod Pathol. 2004 Apr;17(4):423-9.Abstract quote Surrogate light chains consisting of VpreB (CD179a) and lambda5 (CD179b) are expressed in precursor B cells lacking a complete form of immunoglobulin and are thought to act as substitutes for conventional light chains. Upon differentiation to immature and mature B cells, CD179a/b disappear and are replaced with conventional light chains. Thus, these molecules may be useful as essential markers of precursor B cells. To examine the expression of the surrogate light-chain components CD179a and CD179b in precursor B-cell lymphoblastic lymphoma, we analyzed tissue sections using immunohistochemistry techniques. Among a number of monoclonal antibodies for the surrogate light chains, VpreB8 and SL11 were found to detect CD179a and CD179b, respectively, in acetone-fixed fresh frozen sections. Moreover, we also observed VpreB8 staining in formalin-fixed, paraffin-embedded sections. Using these antibodies, we found that CD179a/b were specifically expressed in precursor B-cell lymphoblastic lymphomas, but not in mature B-cell lymphomas in childhood. Furthermore, other pediatric tumors that must be included in a differential diagnosis of precursor B-cell lymphoblastic lymphoma, including precursor T-cell lymphoblastic lymphoma, extramedullary myeloid tumors, and Ewing sarcoma, were also negative for both CD179a and CD179b. Our data indicate that CD179a and CD179b may be important markers for the immunophenotypic diagnosis of precursor B-cell lymphoblastic lymphomas.
MYELOPEROXIDASE
Myeloperoxidase Immunoreactivity in Adult Acute Lymphoblastic Leukemia Daniel A. Arber, MD, David S. Snyder, MD, Miriam Fine, MS, Andrew Dagis, MS, Joyce Niland, PhD, and Marilyn L. Slovak, PhD	Am J Clin Pathol 2001;116:25-33 Abstract quote To evaluate the frequency and significance of myeloperoxidase positivity in adult acute lymphoblastic leukemia (ALL), bone marrow biopsy material from 82 adults with ALL was evaluated with a polyclonal myeloperoxidase (pMPO) antibody. Nineteen cases (23%) demonstrated evidence of pMPO immunoreactivity. Positive cases were precursor B-cell lineage, and CD13 or CD15 expression was more frequent than in the pMPO-negative cases. A subset of pMPO-positive cases studied with a monoclonal MPO antibody was negative. Western blot analysis using the pMPO antibody showed the expected 55-kd band for myeloperoxidase in pMPO-positive and pMPO-negative ALLs, suggesting a lack of specificity of this antibody in ALL. Forty-two percent (8/19) of the pMPO-positive ALL cases demonstrated evidence of t(9;22) by either karyotype or polymerase chain reaction analysis. The pMPO-positive ALLs had a lower frequency of extramedullary disease than the pMPO-negative group and a trend toward improved overall survival compared with the pMPO-negative group. Immunoreactivity with pMPO in adult ALL may lead to an incorrect interpretation of biphenotypic acute leukemia using a recently described scoring system, and a revision to that scoring system is proposed to accommodate pMPO-positive ALL.
PODOCALYXIN
Podocalyxin A Marker of Blasts in Acute Leukemia Todd W. Kelley, MD, etal.	Am J Clin Pathol 2005;124:134-142 Abstract quote Podocalyxin is a CD34 family member expressed by podocytes, vascular endothelium, mesothelium, and a subset of hematopoietic progenitors. Podocalyxin expression was not observed in the hematopoietic cells of normal adult bone marrow samples. However, podocalyxin was expressed by blasts in 30 (77%) of 39 cases of acute myeloid leukemia (AML), 22 (81%) of 27 cases of acute lymphoblastic leukemia (ALL), and 13 (87%) of 15 cases of cutaneous myeloid sarcoma. No correlation with CD34 expression by immunohistochemical analysis was seen. Wilms tumor 1 (WT1) expression was detected in blasts in 17 AML cases (44%) and 21 ALL cases (78%). There was no correlation between WT1 and podocalyxin expression. We conclude that podocalyxin is expressed commonly by blasts in ALL and AML. Analysis of the expression of CD34 and podocalyxin increases sensitivity for the immunophenotypic detection of leukemic blasts compared with the analysis of CD34 alone. Therefore, podocalyxin seems to complement CD34 as a useful hematopoietic blast marker. The physiologic role of podocalyxin in leukemic blasts remains unknown.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Favorable Prognostic Factors
Age	1-10 years
Sex	Female
Race	White
WBC	<10x10*9/L
Rapidity of cytoreduction	Bone marrow free of disease by day 14
Relapse	No relapse
Morphology	LI
Immunophenotypic	Early B-cell precursor CD10+ (CALLA positive)
Cytogenetic	Hyperdiploidy>50 chromosomes
Unfavorable Prognostic Factors
Age	<1 and >10 years
Sex	Male
Race	Black
WBC	>50x10*9/L
Rapidity of cytoreduction	Residual disease by day 14
Relapse	Relapse
Morphology	L2, L3
Immunophenotypic	Pre-B-cell (CIg+) CD10- (CALLA negative) T-cell ALL B-cell ALL
Cytogenetic	Translocations, including t(9;22) and t(4;11)
5 Year Survival
B-cell precursor	Chemotherapy with CNS prophylaxis and maintenance therapy results in remission in >95% of cases and >50% long-term disease free survival Postinduction chemotherapy leads to cure rates of 70%
High risk types including T-cell ALL	Long term disease free survival of 40-50%
Metastasis	Relapse occurs in: Testicles Brain and spinal cord
Changes that may occur with relapse	L1 to L2 morphology TdT positive to negative Gain or loss of an antigen Clonal evolution in 75% with one or more new structural abnormalities Lineage switch to myeloid leukemia often related to therapy and associated with 11q23 chromosome abnormality
ADDITIONAL PROGNOSTIC FACTORS
CEREBROSPINAL FLUID
Molecular monitoring of cerebrospinal fluid can predict clinical relapse in acute lymphoblastic leukemia with eosinophilia. Nunez CA, Zipf TF, Roberts WM, Medeiros LJ, Hayes K, Bueso-Ramos CE. Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.	Arch Pathol Lab Med 2003 May;127(5):601-5 Abstract quote In a patient with precursor B-cell acute lymphoblastic leukemia (ALL) associated with eosinophilia that completely responded to induction chemotherapy, we assayed serial remission cerebrospinal fluid and bone marrow specimens for minimal residual disease using a quantitative polymerase chain reaction assay to assess for clone-specific immunoglobulin heavy-chain gene cluster (IGH) gene rearrangement. Cerebrospinal fluid eosinophilia and minimal residual disease were detected on day 406, preceding the morphologic diagnosis of central nervous system relapse on day 578. By day 841, the bone marrow had 35% blasts. Despite aggressive therapy, including unrelated umbilical cord blood transplantation, the patient developed testicular and bone marrow relapses and died of disease. We conclude that increasing levels of minimal residual disease in cerebrospinal fluid can predict recurrence of ALL prior to clinical and morphologic relapse. Furthermore, we demonstrate a novel translocation in this tumor, the t(5;9)(q31;p24), that possibly led to fusion of the interleukin-3 (IL3) (5q31) and JAK2 (9p24) genes and may explain the concomitant appearance of eosinophilia and ALL.
Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia. Howard SC, Gajjar AJ, Cheng C, Kritchevsky SB, Somes GW, Harrison PL, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, De Armendi AJ, Razzouk BI, Pui CH. Department of Hematology/Oncology, Barry-Longinotti Bldg, Room S2014C, 332 N Lauderdale St, Memphis, TN 38105-2794.	JAMA 2002 Oct 23;288(16):2001-7 Abstract quote CONTEXT: Traumatic or bloody lumbar puncture (LP) reduces the diagnostic value of the procedure and may worsen the outcome of patients with acute lymphoblastic leukemia (ALL). Little is known about the risk factors for traumatic and bloody LP. OBJECTIVES: To determine the risk factors for traumatic and bloody LP. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 956 consecutive patients with newly diagnosed childhood ALL who were treated at a pediatric cancer center between February 1984 and July 1998. INTERVENTIONS: All patients underwent a diagnostic LP followed by a median of 4 LPs to instill intrathecal chemotherapy. MAIN OUTCOME MEASURE: Traumatic LP was defined as an LP in which cerebrospinal fluid contained at least 10 red blood cells (RBCs) per microliter and bloody LP as one in which the cerebrospinal fluid contained at least 500 RBCs per microliter. RESULTS: Of the 5609 LPs evaluated, 1643 (29%) were traumatic and 581 (10%) were bloody. The estimated odds ratios (ORs) and 95% confidence intervals (CIs) for traumatic LP were 1.5 (95% CI, 1.2-1.8) for black vs white race, 2.3 (95% CI, 1.7-3.0) for age younger than 1 year vs 1 year or older, 1.4 (95% CI, 1.2-1.7) for early vs recent (dedicated procedure area and general anesthesia) treatment era, 1.5 (95% CI, 1.2-1.8) for platelet count of 100 x 10(3)/ micro L or more vs less than 100 x 10(3 )/ micro L, 10.8 (95% CI, 7.7-15.2) for short (1 day) vs longer (>15 days) interval since the previous LP, and 1.4 (95% CI, 1.1-1.8) for the least vs the most experienced practitioners. Analyses for bloody LP yielded similar results. CONCLUSIONS: The unmodifiable risk factors for traumatic and bloody LP include black race, age younger than 1 year, a traumatic or bloody previous LP performed within the past 2 weeks, and a previous LP performed when the platelet count was 50 x 10(3)/ micro L or less. Modifiable risk factors include procedural factors reflected in treatment era, platelet count of 100 x 10(3)/ micro L or less, an interval of 15 days or less between LPs, and a less experienced practitioner.
PHILADELPHIA CHROMOSOME
Acute Lymphoblastic Leukemia in Elderly Patients The Philadelphia Chromosome May Not Be a Significant Adverse Prognostic Factor Mihaela Onciu, MD Carlos Bueso-Ramos, MD, PhD L. Jeffrey Medeiros, MD Greg Ball, MS Terry Smith, MS Raymond Lai, MD, PhD	Am J Clin Pathol 2002;117:716-720 Abstract quote Acute lymphoblastic leukemia (ALL) in elderly patients (59 years or older) carries a poor prognosis, and this finding may be attributed to the relatively high frequency of the Philadelphia chromosome (Ph). To test this hypothesis, we reviewed the clinicopathologic features of 23 consecutive, newly diagnosed elderly patients with ALL (14 men, 9 women, aged 59-92 years) uniformly treated at our institution and compared the Ph+ and Ph– groups. Conventional cytogenetic data were available for 21 of 23 cases; 7 (33%) were Ph+. All Ph+ cases were of precursor B-cell type. The remaining 16 tumors were of precursor B-cell (10), mature B-cell (2), precursor T-cell (3), and mixed precursor T-cell/B-cell (1) type. Ph+ and Ph– groups did not differ significantly in median survival (13.4 months vs 19.0 months) or other variables studied. The Ph may not be a significant adverse prognostic factor in ALL in elderly patients.
TREATMENT	Combination chemotherapy with CNS prophylaxis and maintenance therapy Allogeneic bone marrow transplantation following first remission in children with high risk ALL and for relapse following standard chemotherapy

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