Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-06-02T13:18:19.455Z Has data issue: false hasContentIssue false

6 - Acute Lymphoid Leukaemias (ALL) and Minimal Residual Disease in ALL

Published online by Cambridge University Press:  01 February 2018

Anna Porwit
Affiliation:
Lunds Universitet, Sweden
Marie Christine Béné
Affiliation:
Université de Nantes, France
Get access

Summary

Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2018

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Conter, V., Aricò, M., Basso, G., et al. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia. Leukemia, 24 (2010), 255–64.CrossRefGoogle ScholarPubMed
Möricke, A., Zimmermann, M., Reiter, A., et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia, 24 (2010), 265–84.CrossRefGoogle Scholar
Pui, C-H., Carroll, W.L., Meshinchi, S., et al. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol, 29 (2011), 551–65.CrossRefGoogle ScholarPubMed
Pui, C-H., Pei, D., Campana, D., et al. A revised definition for cure of childhood acute lymphoblastic leukemia. Leukemia, 28 (2014), 2336–43.CrossRefGoogle ScholarPubMed
Mullighan, C.G.. Genomic characterization of childhood acute lymphoblastic leukemia. Semin Hematol, 50 (2013), 314–24.CrossRefGoogle ScholarPubMed
Chiaretti, S., Gianfelici, V., Ceglie, G., et al. Genomic characterization of acute leukemias. Med Princ Pract, 23 (2014), 487506.CrossRefGoogle ScholarPubMed
Bennett, J.M., Catovsky, D., Daniel, M.T., et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol, 33 (1976), 451–8.CrossRefGoogle ScholarPubMed
Swerdlow, S.H., Campo, E., Harris, N.L., et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (IARC, WHO PRESS, 4th Edition, 2008).Google Scholar
Gaipa, G., Basso, G., Biondi, A., et al. Detection of minimal residual disease in pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom, 84 (2013), 359–69.CrossRefGoogle ScholarPubMed
Craig, F.E. and Foon, K.A.. Flow cytometric immunophenotyping for hematologic neoplasms. Blood, 111 (2008), 3941–67.CrossRefGoogle ScholarPubMed
Bene, M.C., Castoldi, G., Knapp, W., et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia, 9 (1995), 1783–6.Google Scholar
Schultz, K.R., Bowman, W.P., Aledo, A., et al. Improved early event-free survival with imatinib in Philadelphia chromosome–positive acute lymphoblastic leukemia: A Children's Oncology Group Study. J Clin Oncol, 27 (2009), 5175–81.CrossRefGoogle ScholarPubMed
Mullighan, C.G.. The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program 2014 (2014), 174–80.CrossRefGoogle ScholarPubMed
Basso, G., Buldini, B., De Zen, L., et al. New methodologic approaches for immunophenotyping acute leukemias. Haematologica, 86 (2001), 675–92.Google ScholarPubMed
Borowitz, M.J., Guenther, K.L., Shults, K.E., et al. Immunophenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis. Am J Clin Pathol, 100 (1993), 534–40.CrossRefGoogle ScholarPubMed
Wood, B.L.. Flow cytometry in the diagnosis and monitoring of acute leukemia in children. J Hematopathol, 8 (2015):191–9.CrossRefGoogle Scholar
Wood, B.L., Arroz, M., Barnett, D., et al. Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia. Cytometry B Clin Cytom, 72 Suppl 1 (2007), S1422.CrossRefGoogle ScholarPubMed
Dworzak, M.N., Buldini, B., Gaipa, G., et al. AIEOP-BFM Consensus guidelines 2014 for flow cytometric immunophenotyping of pediatric acute lymphoblastic leukemia: standard development and validation of interpretation. Cytometry B Clin Cytom, (2017) February 10. doi: 10.1002/cyto.b.21518. [Epub ahead of print].Google Scholar
Al-Seraihy, A.S., Owaidah, T.M., Ayas, M., et al. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica, 94 (2009), 1682–90.CrossRefGoogle ScholarPubMed
Gerr, H., Zimmermann, M., Schrappe, M., et al. Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. Br J Haematol, 149 (2010), 8492.CrossRefGoogle ScholarPubMed
Coustan-Smith, E., Mullighan, C.G., Onciu, M., et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol, 10 (2009), 147–56.CrossRefGoogle ScholarPubMed
Inukai, T., Kiyokawa, N., Campana, D., et al. Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15. Br J Haematol, 156 (2012), 358–65.CrossRefGoogle Scholar
Conter, V., Valsecchi, M.G., Buldini, B. et al. Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis. Lancet Haematol, 3 (2016), e806.CrossRefGoogle ScholarPubMed
Patrick, K., Wade, R., Goulden, N., et al. Outcome for children and young people with early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol, 166 (2014), 421–4.CrossRefGoogle Scholar
Wood, B., Winter, S.S., Dunsmore, K.P., et al. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early thymic precursor (ETP) immunophenotype and validation of the prognostic value of end-induction minimal residual disease (MRD) in Children's Oncology Group (COG) study AALL0434. Blood, 124 (2014), 1 ASH Abstract.CrossRefGoogle Scholar
Jain, N., Lamb, A.V., O'Brien, S. et al. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood, 127 (2016), 1863–9.CrossRefGoogle ScholarPubMed
Hrusak, O., Basso, G., Ratei, R., et al. Flow diagnostics essential code: a simple and brief format for the summary of leukemia phenotyping. Cytometry B Clin Cytom, 86 (2014), 288–91.CrossRefGoogle Scholar
Chiaretti, S., Vitale, A., Cazzaniga, G., et al. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica, 98 (2013), 1702–10.CrossRefGoogle ScholarPubMed
Hrusák, O. and Porwit-MacDonald, A.. Antigen expression patterns reflecting genotype of acute leukemias. Leukemia, 16 (2002), 1233–58.CrossRefGoogle ScholarPubMed
Basso, G., Case, C. and Dell'Orto, M.C.. Diagnosis and genetic subtypes of leukemia combining gene expression and flow cytometry. Blood Cells Mol Dis, 39 (2007), 164–8.CrossRefGoogle ScholarPubMed
Bernt, K.M. and Hunger, S.P.. Current concepts in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. Front Oncol, 4 (2014), 54.CrossRefGoogle ScholarPubMed
Aricò, M., Schrappe, M., Hunger, S.P., et al. Clinical outcome of children with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol, 28 (2010), 4755–61.CrossRefGoogle ScholarPubMed
Tabernero, M.D., Bortoluci, A.M., Alaejos, I., et al. Adult precursor B-ALL with BCRABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34 CD13 and CD38 expression. Leukemia, 15 (2001), 406–14.CrossRefGoogle Scholar
Kiyokawa, N., Iijima, K., Tomita, O., et al. Significance of CD66c expression in childhood acute lymphoblastic leukemia. Leuk Res, 38 (2014), 42–8.CrossRefGoogle ScholarPubMed
Primo, D., Tabernero, M.D., Perez, J.J., et al. Genetic heterogeneity of BCR/ABL1 adult B-cell precursor acute lymphoblastic leukemia: impact on the clinical, biological and immunophenotypical disease characteristics. Leukemia, 19 (2005), 713–20.CrossRefGoogle Scholar
Buldini, B., Zangrando, A., Michielotto, B., et al. Identification of immunophenotypic signatures by clustering analysis in pediatric patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Am J Hematol, 85 (2010), 138–41.CrossRefGoogle ScholarPubMed
Muntean, A.G. and Hess, J.L.. The pathogenesis of mixed-lineage leukemia. Annu Rev Pathol, 7 (2012), 283301.CrossRefGoogle ScholarPubMed
Slany, R.K.. The molecular biology of mixed lineage leukemia. Haematologica, 94 (2009), 984–93.CrossRefGoogle ScholarPubMed
De Zen, L., Bicciato, S., te Kronnie, G., et al. Computational analysis of flow-cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification. Leukemia, 17 (2003), 1557–65.Google ScholarPubMed
Zangrando, A., Intini, F. F, G. te Kronnie, et al. Validation of NG2 antigen in identifying BP-ALL patients with MLL rearrangements using qualitative and quantitative flow cytometry: a prospective study. Leukemia, 22 (2008), 858–61.CrossRefGoogle Scholar
Attarbaschi, A., Mann, G., König, M., et al. Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity. Clin Cancer Res, 12 (2006), 2988–94.CrossRefGoogle ScholarPubMed
Pui, C-H., Robison, L.L. and Look, A.T.. Acute lymphoblastic leukaemia. Lancet, 371 (2008), 1030–43.CrossRefGoogle Scholar
Fuka, G., Kauer, M., Kofler, R., et al. The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression. PLoS One, 6 (2011), e26348.CrossRefGoogle ScholarPubMed
Linka, Y., Ginzel, S., Krüger, M., et al. The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods. Blood Cancer J, 3 (2013), e151.CrossRefGoogle ScholarPubMed
Morrow, M., Horton, S., Kioussis, D., et al. TEL-AML1 promotes development of specific hematopoietic lineages consistent with preleukemic activity. Blood, 103 (2004), 3890–6.CrossRefGoogle ScholarPubMed
Hrusák, O., Trka, J., Zuna, J., et al. Aberrant expression of KOR-SA3544 antigen in childhood acute lymphoblastic leukemia predicts TEL-AML1 negativity. The Pediatric Hematology Working Group in the Czech Republic. Leukemia, 12 (1998), 1064–70.CrossRefGoogle Scholar
De Zen, L., Orfao, A., Cazzaniga, G., et al. Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification. Leukemia, 14 (2000), 1225–31.CrossRefGoogle ScholarPubMed
Russell, L.J., Capasso, M., Vater, I., et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood, 114 (2009), 2688–98.CrossRefGoogle ScholarPubMed
Mullighan, C.G., Collins-Underwood, JR., Phillips, L.A., et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet, 41 (2009), 1243–6.CrossRefGoogle ScholarPubMed
Chapiro, E., Russell, L., Lainey, E., et al. Activating mutation in the TSLPR gene in B-cell precursor lymphoblastic leukemia. Leukemia, 24 (2010), 642–5.CrossRefGoogle ScholarPubMed
Tasian, S.K., Doral, M.Y., Borowitz, M.J., et al. Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Blood, 120 (2012), 833–42.CrossRefGoogle ScholarPubMed
Bercovich, D., Ganmore, I., Scott, L.M., et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet, 372 (2008), 1484–92.CrossRefGoogle ScholarPubMed
Mullighan, C.G., Zhang, J., Harvey, R.C., et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. PNAS, 106 (2009), 9414–18.CrossRefGoogle ScholarPubMed
Kearney, L., Gonzalez De Castro, D., Yeung, J., et al. A specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukaemia. Blood, 113 (2008), 646–8.Google Scholar
Bugarin, C., Sarno, J., Palmi, C. et al. Fine tuning of surface CRLF2 expression and its associated signaling profile in childhood B-cell precursor acute lymphoblastic leukemia. Haematologica, 100 (2015), e22932.CrossRefGoogle ScholarPubMed
Palmi, C., Vendramini, E., Silvestri, D., et al. Poor prognosis for P2RY8-CRLF2 fusion but not for CRLF2 over-expression in children with intermediate risk B-cell precursor acute lymphoblastic leukemia. Leukemia, 26 (2012), 2245–53.CrossRefGoogle Scholar
Palmi, C., Savino, A.M., Silvestri, D. et al. CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia. Oncotarget, 7 (2016) 59260–72.CrossRefGoogle ScholarPubMed
Germano, G., Pigazzi, M., Del Giudice, L., et al. Two consecutive immunophenotypic switches in a child with MLL-rearranged acute lymphoblastic leukemia. Haematologica, 91 (2006), 2931.Google Scholar
Slamova, L., Starkova, J., Fronkova, E., et al. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia, 28 (2014), 609–20.CrossRefGoogle Scholar
Coustan-Smith, E., Sancho, J., Behm, F.G., et al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood, 100 (2002), 52–8.CrossRefGoogle ScholarPubMed
Conter, V., Bartram, C.R., Valsecchi, M.G., et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood, 115 (2010), 3206–14.CrossRefGoogle ScholarPubMed
Bruggemann, M., Schrauder, A., Raff, T., et al. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia, 24 (2010), 521–35.CrossRefGoogle ScholarPubMed
Dworzak, M.N., Gaipa, G., Ratei, R., et al. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: multicentric assessment is feasible. Cytometry Part B, 74B (2008), 331–40.CrossRefGoogle Scholar
van Dongen, J.J., Lhermitte, L., Bottcher, S., et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia, 26 (2012), 1908–75.CrossRefGoogle ScholarPubMed
Lucio, P., Parreira, A., van den Beemd, M.W., et al. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia, 13 (1999), 419–27.CrossRefGoogle ScholarPubMed
Veltroni, M., De Zen, L., Sanzari, M.C., et al. Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia. Haematologica, 88 (2003), 1245–52.Google ScholarPubMed
Chen, J.S., Coustan-Smith, E., Suzuki, T., et al. Identification of novel markers for monitoring minimal residual disease in acute lymphoblastic leukemia. Blood, 97 (2001), 2115–20.CrossRefGoogle ScholarPubMed
Coustan-Smith, E., Song, G., Clark, C., et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood, 117 (2011), 6267–76.CrossRefGoogle ScholarPubMed
Sutton, R., Venn, N.C., Tolisano, J., et al. Clinical significance of minimal residual disease at day 15 and at the end of therapy in childhood acute lymphoblastic leukaemia. Br J Haematol, 146 (2009), 292–9.CrossRefGoogle ScholarPubMed
Ratei, R., Basso, G., Dworzak, M., et al. Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction. Leukemia, 23 (2009), 528–34.CrossRefGoogle ScholarPubMed
Basso, G., Veltroni, M., Valsecchi, M.G., et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol, 27 (2009), 5168–74.CrossRefGoogle ScholarPubMed
Eckert, C., von Stackelberg, A., Seeger, K., et al. Minimal residual disease after induction is the strongest predictor of prognosis in intermediate risk relapsed acute lymphoblastic leukaemia - long-term results of trial ALL-REZ BFM P95/96. Eur J Cancer, 49 (2013), 1346–55.CrossRefGoogle ScholarPubMed
Volejnikova, J., Mejstrikova, E., Dörge, P., et al. Ikaros (IKZF1) alterations and minimal residual disease at day 15 assessed by flow cytometry predict prognosis of childhood BCR/ABL-negative acute lymphoblastic leukemia. Pediatr Blood Cancer, 60 (2013), 420–7.CrossRefGoogle ScholarPubMed
Eveillard, M., Robillard, N., Arnoux, I., et al. Major impact of an early bone marrow checkpoint (day 21) for minimal residual disease in flow cytometry in childhood acute lymphoblastic leukemia. Hematol Oncol, 35 (2017):237–43.CrossRefGoogle ScholarPubMed
Gaipa, G., Cazzaniga, G., Valsecchi, M.G., et al. Time point-dependent concordance of flow cytometry and real-time quantitative polymerase chain reaction for minimal residual disease detection in childhood acute lymphoblastic leukemia. Haematologica, 97 (2012), 1582–93.CrossRefGoogle ScholarPubMed
Paganin, M., Fabbri, G., Conter, V., et al. Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia. J Clin Oncol, 32 (2014), 3553–8.CrossRefGoogle ScholarPubMed
Stary, J., Zimmermann, M., Campbell, M., et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol, 32 (2014), 174–84.CrossRefGoogle ScholarPubMed
Nachman, J.B., Heerema, N.A., Sather, H., et al. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood, 110 (2007), 1112–5.CrossRefGoogle ScholarPubMed
Charrin, C., Thomas, X., French, M., et al. A report from the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL). Blood, 104 (2004), 2444–51.CrossRefGoogle ScholarPubMed
Shaffer, L.G., McGowan-Jordan, J. and Schmid, M.. ISCN 2013 – An International System for Human Cytogenetic Nomenclature (Karger, Basel, 2013).Google Scholar
Look, A.T., Roberson, P.K., Williams, D.L., et al. Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia. Blood, 65 (1985), 1079–86.CrossRefGoogle ScholarPubMed
Pui, C-H., Dodge, R.K., Look, A.T., et al. Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X. J Clin Oncol, 9 (1991), 1341–7.CrossRefGoogle ScholarPubMed
Aricò, M., Valsecchi, M.G., Rizzari, C., et al. Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol, 26 (2008), 283–9.CrossRefGoogle ScholarPubMed
Trueworthy, R., Shuster, J., Look, T., et al. Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol, 10 (1992), 606–13.CrossRefGoogle ScholarPubMed
Chilton, L., Hills, R.K., Harrison, C.J., et al. Hyperdiploidy with 49-65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome. Leukemia, 28 (2014), 321–8.CrossRefGoogle ScholarPubMed
Holmfeldt, L., Wei, L., Diaz-Flores, E., et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet, 45 (2013), 242–52.CrossRefGoogle ScholarPubMed
Ito, C., Kumagai, M., Manabe, A., et al. Hyperdiploid acute lymphoblastic leukemia with 51 to 65 chromosomes: a distinct biological entity with a marked propensity to undergo apoptosis. Blood, 93 (1999), 315–20.CrossRefGoogle ScholarPubMed
Rachieru-Sourisseau, P., Baranger, L., Dastugue, N. et al. DNA Index in childhood acute lymphoblastic leukaemia: a karyotypic method to validate the flow cytometric measurement. Int J Lab Hematol, 32 (2010), 288–98.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×