A Limited Course of Eculizumab in a Child with the Atypical Hemolytic Uremic Syndrome and Pre-B Acute Lymphoblastic Leukemia on Maintenance Therapy: Case Report and Literature Review

Abstract

Acute lymphoblastic leukemia (ALL) is considered a possible risk for the occurrence of thrombotic microangiopathies. We present a girl with pre-B ALL successfully treated according to the BFM ALL IC-2009 protocol on maintenance therapy followed by aHUS occurrence. This is the seventh case of HUS/aHUS on ALL maintenance therapy and the first with clearly documented eculizumab use in the early stage of aHUS/secondary TMA. Standard and additional parameters were used in aHUS monitoring alongside the reticulocyte production index adjusted for age (RPI/A) and the aspartate aminotransferase-to-platelet ratio index (APRI) as markers of hemolysis and rapid response following treatment. RPI/A and APRI are markers of bone marrow response to anemia serving as red blood cell vs. platelet recovery markers. Together they mark the exact recovery point of thrombotic microangiopathy and serve as a prognostic marker of eculizumab treatment success. During the 8-month treatment and 6-month follow-up, no recurrence of hemolysis, ALL relapse, or renal damage were observed. A systematic review of the literature revealed 14/312 articles; five children had aHUS before the onset of ALL, and two children had both diseases concurrently. At least 3/7 patients are attributed to aHUS, of whom 2/7 have renal damage. Potential undiagnosed/unpublished cases may be assumed.

Thrombotic Microangiopathy Due to Progressive Disseminated Histoplasmosis in a Child With Down Syndrome and Acute Lymphoblastic Leukemia

“…Nonetheless, cases of recurrent hemolytic uremic syndrome (a subset of TMA) have been reported in other children receiving ALL maintenance therapy. [12][13][14] Vincristine was the suspected cause for one child. 12 Another child was found to have a potential genetic predisposition with homozygosity for the CFH H3 haplotype, though 6-mercaptopurine was felt to be an additional trigger; she was successfully treated with eculizumab.…”

Complement-Mediated Thrombotic Microangiopathy with 10 Years of Stable Renal Function After a Year-Long Treatment with Eculizumab with Coincidental Polycystic Kidney Disease

“…It is unknown whether earlier treatment with eculizumab would have helped her renal function to recover fully and whether it helped her to come off hemodialysis. Eculizumab therapy very effectively reverses unchecked complement activation and reduces death from cTMA [6][7][8]. Initial guidelines suggested that treatment should be lifelong.…”

“…No advice was given on how to proceed when a patient was stable and in remission. Lack of proven cTMA disease activity does not denote complete renal recovery [6][7][8][9]. In addition, the recurrence or progressive rate of cTMA varies for each mutation, so lifelong continuation may be unnecessary for some.…”

“…We present an alternative method that some have utilized [7,8], of intensive clinical monitoring after completing eculizumab treatment for cTMA for a year and achieving a clinical remission. This intensive followup care strategy was possible because of a reliable family that understood the risks of this illness.…”

“…By blocking unchecked complement 3 activation, endothelial injury can be prevented. Eculizumab is very effective in the treatment of cTMA, but based on current scientific data, it is recommended to be taken as a lifelong treatment [5][6][7][8][9].…”