Bisphosphonate treatment in children with acute lymphoblastic leukemia and osteonecrosis – radiological and clinical findings in a national cohort

Figures & data

Table 1. Patient and treatment characteristics of the pediatric patients with pre-B-ALL and osteonecrosis treated with bisphosphonates (N = 10).

Pat.	Diagnosis	Sex	Age at leukemia dg	Treatment protocol	HSCT (+/−) GVHD (+/−)	Age at ON dg	No of ON lesions	Highest ON grade at dg	BP treatment; duration	BP treatment; timing	Surgery	Pain
1	Pre-B-ALL; secondary AML	Male	5.8	NOPHO-ALL 1992 HR + NOPHO-AML	HSCT +; twice No GVHD nor glucocorticoids after 2. HSCT	16.1 (3 years 5 months after 2. HSCT)	6	4	Pamidronate iv; duration 2.3 years	After treatment	Yes; Hip arthroplasty	Pain was significantly relieved after 1 year of BP treatment
2	Pre-B-ALL	Male	14.8	NOPHO-ALL 1992 HR	HSCT + GVHD +  needing glucocorticoids for 7 months	16.9 (16 months after HSCT)	2	5	Pamidronate iv; 0.3 years (2 doses)	After treatment	–	No clear effect on pain
3	Pre-B-ALL	Female	5.1	NOPHO-ALL 2008 SR	–	5.8	1	2	Pamidronate iv; 1.8 years	During leukemia treatment; at first maintenance (1 year into treatment)	–	Pain was relieved within 2 months after the first BP infusion
4	Pre-B-ALL	Male	14.5	NOPHO-ALL 1992 IR & NOPHO-ALL 2000 HR (relapse)	HSCT +; after relapse; GVHD needing glucocorticoids for 4 months	20.8 (25 months after HSCT)	2	5	Pamidronate iv; 1.4 years, then alendronate po for 2 years	After treatment	Yes; Hip arthroplasty (operation planned before BP treatment)	Hip joint operation soon after BP start – the effect of BP cannot be evaluated Pain in other joints ameliorated during the 2 years into BP treatment
5	Pre-B-ALL	Female	17.7	NOPHO-ALL 2008 SR	–	18.2	6	4	Alendronate po; 4.1 years	During leukemia treatment; after 10 months into leukemia treatment), at maintenance 1	–	Pain was significantly relieved after ∼1.5 years of BP treatment
6	Pre-B-ALL	Female	14.0	NOPHO-ALL 2008 SR -> HR	–	14.0 (At diagnosis)	9	4	Alendronate po; 3.6 years	During ALL treatment; from induction through the whole leukemia treatment	–	Pain disappeared between 3 and 9 months after BP start
7	Pre-B-ALL	Male	13.9	NOPHO-ALL 2008 SR	HSCT + No GVHD nor glucocorticoids	15.6 (11 months after HSCT)	2	5	Ibandronate po; 1.3 years	After treatment	Yes; Hip osteotomy	No clear effect on pain
8	Pre-B-ALL	Male	7.8	NOPHO-ALL 2008 SR	–	8.9	7	5	Pamidronate iv; 1.8 years	After completing ALL treatment	–	Pain was only mild at beginning of BPs despite wide-spread, progressive lesions No pain after BP start
9	Pre-B-ALL	Female	2.0	NOPHO-ALL 2008 SR	–	2.8	10	3	Pamidronate iv; 1.8 years	After completing ALL treatment	–	Pain was ameliorated within 5 months of BP treatment, but mild, intermittent pain symptoms continued
10	Pre-B-ALL	Female	12.6	NOPHO-ALL 2008 SR	–	12.9	9	3	Pamidronate iv; 1.0 years	During the ALL treatment; at final maintenance	–	Originally severe pain was significantly relieved after 6 months of BP treatment, and totally disappeared later

ON: osteonecrosis; HSCT: hematopoietic stem cell transplantation; GVHD: graft versus host disease; BP: bisphosphonate; SR: standard risk; HR: high risk; IR: intermediate risk.

Figure 1. (A) Distribution of osteonecrosis (ON) lesions (N = 55) in 10 pediatric ALL patients treated with bisphosphonates. (B) Evolution of the 55 ON lesions with follow-up. Classification grades 1–5 according to Niinimäki classification*. At the last evaluation, 80% (N = 44) of the ON lesions were either regressed to lower stages or were stable, while 20% of the lesions had progressed. Altogether 13 ON lesions (24%) had totally healed. None of the ON lesions that were originally graded 4 or 5 were totally healed. All lesions originally graded as 5 (deformation of joint) remained at grade 5 at the last evaluation. (C) Evolution of ON lesions (a) at the hip (N = 10) and (b) at the knee (N = 8) (c) at the ankle (N = 8) and (d) shoulder (N = 7) according to original grading. *The Niinimäki classification, grades 1–5, is based on the following characteristics of the ON lesions: location (weight-bearing or non-weight-bearing bone; long or short bone; diaphysis-metaphysis-epiphysis), the area of articular surface involvement and deformation of the joint (Ref. [13]; Supplementary Figure 1).

Niinimäki T, Niinimäki J, Halonen J, et al. The classification of osteonecrosis in patients with cancer: validation of a new radiological classification system. Clin Radiol. 2015;70(12):1439–1444.

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