Cases presentation
Patient №1 (Fig 1, a). A 15-year-old boy diagnosed with
X-linked lymphoproliferative syndrome type 1 (deletion in exon 1 of the
SH2D1A gene in the hemizygous state) was transplanted from a
haploidentical donor (father) with TCRαβ+/CD19+ depleted peripheral
hematopoietic stem cells. In the early post-transplantation period (from
Day +12) he experienced an “engraftment syndrome” – maculopapular
rash on the trunk and palmar-plantar erythema equivalent to acute GVHD
stage II, skin-2. The immunosuppression was initiated with
methylprednisolone 2 mg/kg/day for 3 days, taped to 1 mg/kg/day. Against
the background of a decrease in the dose of methylprednisolone, the
patient’s condition worsened from Day +17: progression of the acute GVHD
to stage III (GI-3, skin-3), and upper intestinal lesion with the
development of severe nausea, vomiting, lack of appetite, severe
abdominal pain syndrome requiring morphine. Patient suffered a GI
hemorrhagic syndrome (gastroscopy results). No pathogens were identified
in the feces. The patient’s condition was at risk of infectious
complications due to presence of CMV viremia. On Day +21 the patient was
diagnosed with acute GVHD stage 4 (GI-4, hemorrhagic colitis; skin - 4,
generalized erythroderma). Further, the dose of corticosteroids was
increased, and a multiple correction of the immunosuppressive therapy
was also performed. Ruxolitinib, etanercept, cyclosporine A (CSA), and
alemtuzumab were used at the recommended dosage, without GVHD
improvement. After alemtuzumab (Day +24), there occurred a decrease in
the number of T-cells to 40 cells/µl, followed by their rise to 92 cells
on Day +28, and subsequent growth dynamics.
The multiple immunosuppressive therapy was ineffective, patient’s
condition progressively worsened, there were risks of severe infectious
complications, and leukapheresis was impossible. We have therefore
developed a modification of ECP without leukapheresis, as compassionate
therapy. Since we were well aware that the number of targeted cells
received is extremely small, the ECP schedule was set to 4 procedures
per week.
On Day + 29 we started the micro-ECP therapy. For 5 consecutive weeks,
the patient received 4 micro-ECP treatments per week as described
before. On the second week of micro-ECP therapy GVHD progression
stopped, and on the third week we could already see a clear regression.
The skin manifestations did not worsen and turned into
hyperpigmentation, hemorrhagic colitis completely disappeared, and the
volume of stool decreased. On Day +56 (fourth week of micro-ECP
treatment), the skin syndrome was represented by residual
hyperpigmentation of the chest, abdomen, back, upper limbs; intestinal
syndrome - thick stool once in 2-3 days. The immunosuppressive therapy
and the frequency of micro-ECP procedures were gradually decreased to 1
in 4 weeks by 22 weeks. However, from the Day +320 a folliculitis-like
rash appeared on the abdomen, chest and back (chronic GVHD?) -
methylprednisolone dose was augmented and CSA was changed to
ruxolitinib. The frequency of micro-ECP procedures was increased to 1
per week, followed by a gradual decrease to 1 at 4 weeks to 65 weeks.
The total duration of micro-ECP therapy was 69 weeks. The graft function
is currently satisfactory. There are no signs of progression of chronic
GVHD. Immunosuppressive therapy: ruxolitinib 5 mg x 3 times a day,
prednisolone 2.5 mg x 2 times a day.
Patient №2 (Fig 1, b). A 2-year-old girl diagnosed with
acute myeloid leukemia, M2, t(X;11)(q24;q23) KMT2A/SEPT6 gene after
allogeneic bone marrow transplantation from a haploidentical donor
(father). The early post-transplant period was complicated by mucositis
grade 3, neutropenic enterocolitis. The first signs of acute GVHD
appeared on Day +5 - skin lesions-2, Grade I. Treatment with
methylprednisolone (1mg/kg) and etanercept was started. Despite the
ongoing therapy, from Day +12 progression of acute GVHD with an increase
skin lesions up to grade 3 and elevation of bilirubin (acute GVHD III)
was noted. Immunosuppressive therapy was modified - a short course of
high-dose methylprednisolone (5mg/kg) followed by a gradual reduction;
ruxolitinib was added to therapy for 3 days with a single injection of
tocilizumab (162mg). Against the background of the therapy, GVHD
progressed to generalized erythroderma with the formation of several
small bullae (Grade IV).
The patient also suffered multiple infectious complications: CMV-viremia
(Day +18), treated with ganciclovir 10 mg/kg followed by switching to
foscarnet (for 2 weeks) due to a decrease in neutrophils; COVID-19
associated pneumonia from Day +24, treated with remdesivir. Taking into
account the need to control GVHD and to reduce immunosuppressive therapy
(viral infections, high-risk AML), a course of extracorporeal
photopheresis was indicated. We decided to start micro-ECP course from
Day +27. The response to micro-ECP was obtained in the first week as a
lack of progression of GVHD, in the second week as regression of skin
and liver GVHD. At 4 weeks of micro-ECP, there were no signs of active
GVHD. Subsequently, the immunosuppressive therapy was reduced, and the
frequency of micro-ECP procedures was gradually reduced. There was no
recurrence of GVHD, and after 27 weeks of micro-ECP treatment the
patient was discharged from hospital without immunosuppressive therapy,
and with complete healing of GVHD.