To the Editor,
Anemia is a common feature of multiple myeloma. However,there is scarcity of data on autoimmune hemolytic anemia (AIHA) in multiple myeloma and we will like to share our case [1]. A 39 year old male was referred to our center for weakness, dyspnea on exertion and severe anemia (Hb 56 g/l). Peripheral blood smear showed microspherocytes, schistocytes and nRBCs. WBC, platelets and differential leukocyte counts were normal. His LDH was 346 U/L (normal < 240 U/L) and direct antiglobulin test with IgG + C3d was positive. A diagnosis of autoimmune haemolytic anemia (AIHA) was made and he was started on prednisolone at a dose of 1 mg/kg/day. His liver function tests showed total protein 12.1 g/dl. Serum protein electrophoresis demonstrated M band 8.9 g/dl, serum creatinine was 2.4 mg/dl and Beta 2 microglobulin was 15 mg/l. Bone marrow aspirate revealed 90% plasma cells. He was diagnosed with multiple myeloma ISS stage III. He received 6 cycles of bortezomib, thalidomide and dexamethasone at another healthcare facility and had stable disease without any response when he presented to us again. Then, he received cyclophosphamide, thalidomide and dexamethasone protocol and entered into partial remission after 3 cycles. He was mobilized with cyclophosphamide 1.5 g/m2 and G-CSF and conditioned with melphalan 200 mg/m2 during autologous hematopoietic stem cell transplantation (ASCT). He received a hematopoietic stem cell dose of 3.1 × 106/kg.
He engrafted on day + 11. He developed falling hemoglobin to 6.4 g/dl on Day + 16 which was not adequately responding to packed red blood cell transfusions. Also, his platelets started to fall to 5000/cmm around the same time with epistaxis (Fig. 1). Infective work-up at this time was negative. His direct coombs test was positive 2 + . He was diagnosed with Evan’s syndrome (AIHA + Immune thrombocytopenia) and received methylprednisolone pulses × 3 days followed by high dose dexamethasone 40 mg/day × 4 days. His haemoglobin stabilised after that and he started responding to platelet transfusions. Patient gradually improved and received a tandem ASCT. He continues to be in complete remission 7 years after ASCT (Fig. 2).
Fig. 1.
Hemoglobin and platelet trend during Evans syndrome post autologous stem cell transplant
Fig. 2.
Clinical course of patient. ASCT autologous stem cell transplant, CTD cyclophosphamide, thalidomide and dexamethasone
AIHA is common in lymphoproliferative disorders like CLL and NHL but is rare in myeloma. Only few cases have been reported so far [2–4]. One could argue that myeloma antibodies may bind to RBCs and cause a false positive direct antiglobulin test. However, in our case patient had severe anemia with peripheral smear findings highly suggestive of AIHA suggesting that antibodies were indeed lytic in nature. Wada et al. [5] have documented that immunoglobulin binding to patient’s red blood cells was IgG kappa as has been documented by Kashyap et al. [1] AIHA could present at diagnosis or during relapse. [1] Our patient had few interesting findings. One, it is uncommon to have multiple myeloma at this young age. Secondly, AIHA was the presenting manifestation. Thirdly, after autologous HSCT when patient was recovering from myeloablation, he again had drop in Hb and platelets which recovered only after institution of high dose steroids. It is possible that post transplant immune reconstitution played some role here.
We suggest that multiple myeloma should be kept in differential diagnosis of AIHA. Also, patients with multiple myeloma who need frequent blood transfusions, AIHA should be considered in differential diagnosis.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and Animal Rights
Research involving human participants and/or animals—not applicable.
Informed Consent
Patient gave informed consent for his treatment. This study does not involve any research on humans.
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References
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