Acute myeloid leukaemia

Early indication of successful therapy in acute myeloid leukaemia (AML) using the Sysmex XE-2100 interfaced to the rule-based Sysmex Information System (SIS).

Introduction:
Microscopic review of the peripheral blood film for the presence of blast cells is an important component in the monitoring of acute myeloid leukaemia under treatment. This can prove difficult, particularly in the leucopenic patient. An alternative and more accurate, but also more expensive method to detect blasts would be by flow cytometry using monoclonal antibodies.
 
The two cases presented here, show that routine monitoring for blasts by the Sysmex XE-2100 analyser interfaced to the rule based SIS is possible and is particularly valuable under leucopenic conditions.

Case 1:

Clinical results:

The first patient was admitted in May with a diagnosis of acute myeloid leukaemia (type AML - M1).

Following induction therapy the patient went into complete remission by June .

Analysis results:
This patient’s progress is illustrated by a series of IMI-scattergrams (fig. 1). Initially (05/22) there was a rather compact immature cell population amounting to 66% (9,639 /µL) of the total WBC count. The cells in this population have a small volume and a high nuclear/cytoplasmic ratio. Morphologically these cells were classified as M1-blasts (fig. 2).


IMI-channel 05/22   IMI-channel 06/06   


IMI-channel 06/09   IMI-channel 06/14

      
IMI-channel 06/23     
         
Fig. 1: Monitoring of a patient with AML - M1 with XE-2100 IMI-channel and SIS.
 
Following treatment, a second IMI-scattergram (06/06) indicated a marked reduction in this blast cell population. Persistence of blasts, although in greatly reduced numbers, was confirmed morphologically (fig. 3).


Fig. 2: Two myeloblasts type M1   Fig. 3: Myeloblast type M1

In subsequent analyses, the immature cells in the IMI-channel were completely absent and the total WBC count fell to 470 cells/µL. By 09/23 the WBC count had increased to 800/μL, the IMI-channel showed no immature cells.

With appearance of the blasts flag, the rule based SIS automatically generates the order to prepare a smear for microscopic examination (see fig. 1, rule 54). In the absence of a blast flag (standard Q-flag setting is blast > 1%), the SIS generates the comment "under chemotherapy" and triggers the order to prepare a smear and a recommendation to review the IMI-scattergram and count. (see fig. 1, rule 67).

In subsequent analyses, the immature cells in the IMI-channel were completely absent (zero immature cells from a total of 630/µL WBC), this information generated by SIS rule 67, is a helpfully information, with a greater accuracy than cursory routine microscopy of a peripheral blood smear, which also confirmed "no blasts".

By the end of June the patient was in complete remission with no blast cells and a return to normal haematopoiesis.

 
Case 2:
Clinical analysis:
The second patient is 50 years of age and was admitted in March with a diagnosis of acute myeloid leukaemia (AML - M2). Induction therapy was started immediately and initially there was a good response. However in June relapse occurred with a high concentration of blast cells appearing in the peripheral blood.

Analysis results:
The patient’s progress is illustrated in a series of IMI-scattergrams (fig. 4). The first results from 03/26 show a relatively compact immature cell population (26% of the total WBC count). According to their location in the scattergram these cells have a low volume and a high nuclear/cytoplasmic ratio. Morphologically these cells were classified as M2-blasts (fig. 5).

Under treatment, the leukocyte count fell to 880 cells/µL by 05/19 (fig. 7), however blast cells persisted, albeit in low concentration (14/μL or 1.6%). By 06/27 the patient was in severe relapse.


IMI-channel 02/26
  IMI-channel 04/16


IMI-channel 04/17   IMI-channel 05/03 


IMI-channel 05/19   IMI-channel 06/27

Fig. 4: Monitoring of a patient with an AML - M2 with XE-2100 IMI-channel and Sysmex Information System (SIS).
 
With appearance of a blast flag, SIS automatically generates the order to prepare a smear for microscopic examination (rule 54, see fig. 4).

In absence of a blast flag (standard Q-flag setting is blast > 1%), the SIS generates the comment "under chemotherapy" and triggers the order to prepare a smear and a recommendation to review the IMI-scattergram and count. (Rule 67, see fig. 4).

The IMI count of 12/µL in the same area as the blast population stimulated a more intensive review of the smear for the presence of blast cells. This suspicion was confirmed (fig. 6).


Fig. 5: Two myeloblasts type M2
(Type III blasts)
  Fig. 6: Myeloblast type M2


Fig. 7: The graphic shows nummeric cummulativ results from the SIS screen.


Discussion:
In leucopenic samples the IMI-channel information is a useful adjunct to microscopic examination. Together with the rules inherent in the SIS, it is possible to generate and display this information when clinically appropriate.

Case 2 illustrates this well. Data and rules specified from the IMI-channel indicate that therapy was not successful, since even at a WBC-count of 880/µL blasts were still present in the IMI-channel and as well confirmed on blood smear examination.

Even in the absence of a blast flag (lower then 1%), the comment "under chemotherapy",  generated by the SIS, serve as a reminder to react to the low WBC concentration with the IMI results.

Case 1 shows the IMI-channel results of 06/09 clearly indicating that blast cells are no longer present, with a greater accuracy than cursory routine microscopy of a peripheral blood smear.
 
Both cases show that the XE-SIS concept can be used as a routine tool to monitor and indicate therapy success, or otherwise, in the management of acute leukaemia.

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