19 October 2011 (Wednesday) - Lymphoproliferation

A colleague has prepared a case study for staff to use for CPD purposes. I was dead keen to try this out for myself….

Haemoglobin                14.9  g/dl   (11 to 15) White Blood Cells          14.3  10^9/l (4 to 11) Platelets                  124   10^9/l (150 to 400 Red Blood Cells            5.06  10^12/l(3.8 to 4.8) Haematocrit                0.449 ratio  (0.36 to 0.46) Mean Cell Volume           88.7  fl     (80 to 100) Mean Cell Haemoglobin      29.4  pg     (27 to 32) Mean Cell Haemoglobin Con  33.2  g/dl   (32 to 36) Neutrophils                2.6   10^9/l (2 to 7.5) Lymphocytes                11.2  10^9/l (1.5 to 4) Monocytes                  0.4   10^9/l (0.2 to 1) Eosinophils                0.0   10^9/l (0.02 to 0.5) Basophils                  0.0   10^9/l (0 to 0.1)  ESR                        1     mm/h   (1 to 20) Referred to consultant haematologist: Lymphocytosis with mature lymphoid cells with clumped chromatin. smear cells seen.  c/w  Lymphoproliferative disorder, most probably CLL.

Question 1: Discuss what is meant by Lymphoproliferative Disorder?

Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They are sometimes equated with "immunoproliferative disorders", because of the natural function of lymphocytes, but this classification is arguable.

Examples include;

• follicular lymphoma
• chronic lymphocytic leukemia
• acute lymphoblastic leukemia
• hairy cell leukemia
• lymphomas
• multiple myeloma
• Waldenstrom's_macroglobulinemia
• Autoimmune lymphoproliferative syndrome

Question 2: Illustrate the Immunophenotyping Markers to differentiate between the different Lymphoproliferative disorders.

Taken from http://www.cytometry.com.cn/uploadfile/20062615536162.pdf

Disorder/cell type	Marker
B-cell malignancies/Pan-B-cell antigens	CD19, CD20, CD22, CD79b, Igm, Igd, Igk, Igl
Precursor B-cells	CD1d, CD10, CD34, CD45, CD58, TdT, NG2,
Chronic lymphocytic leukaemia	CD5, CD23, CD38, CD52{, ZAP70
Hairy cell leukaemia	CD11c, CD25, CD103
Follicular lymphoma	CD10
Mantle cell lymphoma	CD5
Diffuse large B-cell lymphoma	CD5, CD10
Burkitt’s lymphoma	CD10, TdT
T-cell malignancies/Pan-T-cell antigens	CD2, CD3, CD4, CD5, CD7, CD8, ab TCR, cd TCR
Precursor T cells	CD1a, TdT, Myeloid markers
T-prolymphocytic leukaemia	CD26, CD52
T-large granular lymphocyte leukaemia	CD16, CD56, CD57
Se´zary syndrome/Mycosis fungoides	CD26
Adult T-cell leukaemia/lymphoma	CD25, HLA-DR
Natural killer cell antigens (and natural killer cell malignancies)	CD2, CD7, CD8, CD16, CD56, CD57

Question 3: Discuss the CLL score.

The CLL score is as described in:

http://www.bcshguidelines.com/documents/Lymphoma_disease_app_bcsh_042010.pdf

CLL immunophenotype scoring system (Delgado, et al 2003)
Marker	Score points 1 0
Smlg CD5 CD23 FMC7 CD22 or CD79b	Weak Strong Positive Negative Positive Negative Negative Positive Weak Strong
Score = or > 4 in 92% of cases of CLL
If <= 3 then exclude mantle cell lymphoma by one or both of: (i) Immunostaining of bone marrow trephine sections or lymph node for nuclear cyclin D1 (ii) FISH for t(11:14) using blood, BM or lymph node. Other lymphoproliferative disorders such as marginal zone, follicular and lymphoplasmacytic lymphomas can usually be distinguished by their immunophenotype. In problematic cases, lymph node or other tissue biopsy may be appropriate if the distinction is clinically important.

A score of four or above is obtained in over 90% of cases of CLL. A lower score should be treated with suspicion, but the diagnosis of CLL cannot be ruled out.

However CD5 positivity is present in most (90%+) cases. If this is absent, then alternative diagnoses should be considered.

CLL scoring should not be confused with clinical staging:

	Rai	Binet		Median survival
Lymphocytosis (>15,000/mm3)	0	-		150 months (12.5 years)
Lymphocytosis plus nodal involvement	I	A	<3 node groups	101-108 months (8.5-9 years)
Lymphocytosis plus organomegaly	II	B	>3 node groups	60-71 months (5-6 years)
Anemia (RBCs)	III Hgb <11 g/dL	C	Hgb <10 g/dL	19-24 months (1.5-2 years)
Lymphocytosis plus thrombocytopenia (platelets)	IV PLT <100	PLT <100,000/mm3

Question 4: Discuss the prognosis of patient of being diagnosed with CLL with reference to Lymphocyte doubling time

Lymphocyte Doubling Time is defined as the period of time needed for lymphocytes to double in number the amount found at diagnosis.

http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19871201)60:11%3C2712::AID-CNCR2820601122%3E3.0.CO;2-1/pdf  quotes that it appears to predict the progression of the disease. Specifically it (and other sources) feel that a doubling in less than a year is of worse prognosis than that of more than a year.

However it doesn’t take long to find doubt cast on the validity of these findings. After all, active therapy will reduce the lymphocyte mass, and consequently prolong the lymphocyte doubling time.