CC BY-NC-ND 4.0 · J Lab Physicians 2023; 15(02): 212-216
DOI: 10.1055/s-0042-1757586
Original Article

Hematogones: The Supreme Mimicker and a Cytomorphological Confounder in Acute Lymphoblastic Leukemia

Kanwaljeet Singh
1   Department of Laboratory Sciences and Molecular Medicine, Army Hospital (R&R), Delhi Cantt, Delhi, India
Dwarika Tiwari
1   Department of Laboratory Sciences and Molecular Medicine, Army Hospital (R&R), Delhi Cantt, Delhi, India
Revanth Boddu
1   Department of Laboratory Sciences and Molecular Medicine, Army Hospital (R&R), Delhi Cantt, Delhi, India
Venkatesan Somasundarum
1   Department of Laboratory Sciences and Molecular Medicine, Army Hospital (R&R), Delhi Cantt, Delhi, India
Kundan Mishra
1   Department of Laboratory Sciences and Molecular Medicine, Army Hospital (R&R), Delhi Cantt, Delhi, India
› Author Affiliations


Objective B-lymphocyte progenitors, namely the hematogones (HGs), may pose problems in morphological assessment of bone marrow, not only during the diagnostic workup but also while evaluating bone marrow for remission status following chemotherapy. Here, we describe a series of 12 cases of acute lymphoblastic leukemia (ALL) that included both B-ALL and T-ALL cases, which were evaluated for remission status and revealed blast-like mononuclear cells in bone marrow in the range of 6 to 26%, which on immunophenotypic analysis turned out to be HGs.

Materials and Methods This is a case series of 12 ALL cases who were undergoing treatment at the Army Hospital (Referral and Research), New Delhi. All these cases were under workup for post-induction status (day 28) and to check for suspected ALL relapse. Bone marrow aspirate (BMA), biopsy, and immunophenotyping were performed. Multicolored flow cytometry was performed using CD10, CD20, CD22, CD34, CD19, and CD38 antibodies panel.

Results BMA assessment of 12 cases revealed a maximum of 26% blastoid cells and a minimum of up to 6%, raising the suspicion of hematological relapse. However, on clinical assessment, these patients were well preserved, with preserved peripheral counts. Hence, marrow aspirates were subjected to flow cytometry using the CD markers panel, as discussed above, which revealed HGs. These cases were followed by minimal residual disease (MRD) analysis that revealed MRD-negative status, further confirming our findings.

Conclusion This case series highlights the importance of morphology and bone marrow immunophenotyping in unveiling the diagnostic dilemma in post-induction ALL patients.

Publication History

Article published online:
20 October 2022

© 2022. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

  • References

  • 1 Lúcio P, Parreira A, van den Beemd MW. 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 1999; 13 (03) 419-427
  • 2 Dworzak MN, Fritsch G, Fleischer C. et al. Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis in pediatric bone marrow. Leukemia 1997; 11 (08) 1266-1273
  • 3 Zheng J, Du W, Yao J. et al. Analysis of hematogones in bone marrow from acute myeloid leukaemia cases posttherapy. Eur J Clin Invest 2013; 43 (11) 1140-1146
  • 4 Caldwell CW, Poje E, Helikson MA. B-cell precursors in normal pediatric bone marrow. Am J Clin Pathol 1991; 95 (06) 816-823
  • 5 Christopeit M, Heiland A, Binder M. et al. Impact of physiological BM CD10+CD19+ B-cell precursors (haematogones) in the post-transplant period in patients with AML. Bone Marrow Transplant 2013; 48 (09) 1257-1259
  • 6 Doki N, Haraguchi K, Hagino T. et al. Clinical impact of hematogones on outcomes of allogeneic hematopoietic stem cell transplantation. Ann Hematol 2015; 94 (12) 2055-2060
  • 7 Honebrink T, Dayton V, Burke MJ. et al. Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia. Biol Blood Marrow Transplant 2012; 18 (06) 930-936
  • 8 Shima T, Miyamoto T, Kikushige Y. et al. Quantitation of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic hematopoietic stem cell transplantation. Blood 2013; 121 (05) 840-848
  • 9 Rimsza LM, Larson RS, Winter SS. et al. Benign hematogone-rich lymphoid proliferations can be distinguished from B-lineage acute lymphoblastic leukemia by integration of morphology, immunophenotype, adhesion molecule expression, and architectural features. Am J Clin Pathol 2000; 114 (01) 66-75
  • 10 Braham Jmili N, Nsaibia S, Jacob MC. et al. Immunophenotypic analysis of bone marrow B lymphocyte precursors (hématogones) by flow cytometry. Clin Lab Sci 2009; 22 (04) 208-215
  • 11 Campana D. Role of minimal residual disease monitoring in adult and pediatric acute lymphoblastic leukemia. Hematol Oncol Clin North Am 2009; 23 (05) 1083-1098 , vii
  • 12 Sędek Ł, Bulsa J, Sonsala A. et al. The immunophenotypes of blast cells in B-cell precursor acute lymphoblastic leukemia: how different are they from their normal counterparts?. Cytometry B Clin Cytom 2014; 86 (05) 329-339
  • 13 Agarwal K, Aggarwal M, Aggarwal VK, Pujani M, Nain M. Increased hematogones in an infant with bicytopenia and leucocytosis: a case report. Cases J 2010; 3: 75
  • 14 McKenna RW, Asplund SL, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) and neoplastic lymphoblasts by 4-color flow cytometry. Leuk Lymphoma 2004; 45 (02) 277-285
  • 15 Lee RV, Braylan RC, Rimsza LM. CD58 expression decreases as nonmalignant B cells mature in bone marrow and is frequently overexpressed in adult and pediatric precursor B-cell acute lymphoblastic leukemia. Am J Clin Pathol 2005; 123 (01) 119-124
  • 16 McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 2001; 98 (08) 2498-2507