• Campath-1H;
  • immune thrombocytopenia purpura;
  • autoimmune neutropenia;
  • red cell aplasia;
  • autoimmune haemolytic anaemia


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

We describe 21 patients with severe and life-threatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4–61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias.

The majority of cases of autoimmune cytopenias, which includes immune thrombocytopenia purpura (ITP), autoimmune haemolytic anaemia, autoimmune neutropenia (AIN) and pure red cell aplasia, will respond to conventional immunosuppressive therapy with or without splenectomy. There is, however, a small group of patients with severe, refractory autoimmune cytopenias who fail to respond to conventional treatment or who have a chronic relapsing illness and suffer life-threatening haemorrhages, infections or anaemia as a result of their respective cytopenias. Further problems include the short- and long-term side-effects of corticosteroids, and the potential toxicity of immunosuppressive and cytotoxic agents such as vincristine, cyclophosphamide and azathioprine which can result in significant morbidity and sometimes mortality. It is in this subgroup of patients with severe life-threatening symptoms that a more aggressive approach, namely immunoablation, has recently been considered, for example using high-dose cyclophosphamide with autologous haemopoietic stem cell rescue (Schmitz et al, 1996). While this approach may be effective, it is also associated with a significant risk of morbidity and mortality.

An alternative and less toxic approach in these patients may be treatment with Campath-1H, a humanized IgG monoclonal antibody specific for the CD52 antigen and present on human lymphocytes and monocytes. The main effect of Campath-1H is on T cells and it results in a prolonged and profound depletion of the CD4 and CD8 subpopulations, particularly the CD4 population (Hale et al, 1990), and this might ‘reset’ the immune system without the need for total immune ablation. To sustain the effect and prevent relapse in the long term, subsequent treatment with a low dose of cyclosporine may be useful. In this study, we have assessed the potential of Campath-1H as an immunosuppressive agent in a series of 21 patients with severe refractory and life-threatening cytopenias.

Patients and methods

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

Patients Between November 1995 and August 2000, 21 patients were treated with Campath-IH. All had a severe form of autoimmune cytopenia (ITP, autoimmune haemolytic anaemia, autoimmune neutropenia and pure red cell aplasia) or various combinations thereof, which had either failed to respond to conventional treatment or had followed a chronic relapsing course (see Tables I and II). Co-existing T-large granular lymphocytic leukaemia was excluded in all patients with autoimmune neutropenia. Prior to the commencement of Campath-1H, the patients' clinical condition was stabilized as much as possible. In particular, Campath-1H was deferred until active infection had been successfully treated. In most patients, acute haemorrhagic episodes were successfully treated prior to commencing Campath-1H treatment, but in one patient this was not possible and Campath-1H was given in the presence of fresh, uncontrolled, widespread subcutaneous and mucosal haemorrhage. Informed consent was obtained from all patients. This study was approved by the local hospital research ethics committee.

Table I.   Patient details.
  Disease duration (months)Previous treatmentAutoantibodies
  1. Pred, prednisolone; IVIg, intravenous immunoglobulin; CSA, cyclosporine; Aza, azathioprine; ATG, antithymocyte globulin; VCR, vincristine; GCSF, granulocyte colony-stimulating factor; cyclophos, cyclophosphamide; HDMP, high-dose methyl prednisolone; neut, neutrophil; PAIg, platelet-associated immunoglobulin; DAGT, direct antiglobulin test.

Autoimmune neutropenia (AIN)
151/Female63Pred, Aza, GCSF, CSA, ATG × 2, IVIgNone detected
327/Male, past history of ITP3Pred, GCSF, splenectomy for ITPAnti-HNA-1a
461/Female20GCSFGran. specific
Autoimmune haemolytic anaemia (AIHA)
571/Male114Pred, Aza, splenectomyDAGT: IgG
655/Female18Pred, AzaIgG
768/Female27Pred, Cyclophos, ChlorambucilC′
849/Female10Pred, Aza, CSA, HDMPC′ + weak IgG
Pure red cell aplasia (PRCA)
948/Female, low-grade B-NHL7·5SplenectomyNone detected
1034/Female, renal allograft32Pred, Aza, CSA, ErythropoietinNone detected
1131/Male79Pred, CSA, AzaNone detected
1248/Female21Pred, CSA, ATG, AzaNone detected
Immune thrombocytopenia purpura (ITP)
1373/Female, with B-NHL27Pred, IVIg, VCR, AzaNot tested
Evan's syndrome
1424/Female13Pred, IVIg, VCR, Aza, splenectomyGpIb/IX, DAGT IgG
1560/Female62Pred, IVIg, Aza, VCRPAIg, DAGT IgG + C′
1615/Female, with SLE42Pred, IVIg, CSA, Cyclophos, Aza, plasma exchange, immunoabsorptionGpIIIa, DAGT IgG + C′
Autoimmune pancytopenia (AIP)
1719/Male107Pred, IVIg, VCR, Aza, plasma exchangeGran. specific, GpIIb/IIIa, DAGT IgG
1855/Male2·5Pred, Aza, VCR, IVIg, splenectomyAnti-HNA-1a, PAIg, DAGT IgG
1928/Male119Pred, GCSFGran. specific, PAIg, DAGT IgG
2039/Male, acquired Glanzmann's20Pred, IVIg, CSA, plasma exchange, immunoabsorption, ATGGpIIb/IIIa, gran. specific
2161/Male51Pred, Aza, CSA, ATG × 2, oxymetholoneNot tested
Table II.   Clinical problems prior to treatment with Campath-1H.
1Recurrent infections, tiredness, severe osteoporosis, vertebral collapse (corticosteroid-induced), agranulocytosis after initial GCSF response
2Recurrent infections, profound tiredness, severe bone pain with GCSF
3Severe systemic infections, chest pain and arrythmias with GCSF
4Recurrent infections and mouth ulcers, severe reactions to GCSF
5Chronic relapsing AIHA, non-insulin-dependent diabetes mellitus (NIDDM) secondary to corticosteroids
6Chronic relapsing AIHA, abnormal liver function with Azathioprine
7Red cell transfusion dependent
8Life threatening intravascular haemolysis
9Red cell transfusion dependent
10Red cell transfusion dependent
11Red cell transfusion dependent, iron overload
12Red cell transfusion dependent, iron overload
13Extensive mucosal and cutaneous haemorrhages
14Severe mucosal and cutaneous haemorrhages, compensated haemolysis
15Purpura, corticosteroid dependent, past history of bronchial carcinoma
16Severe mucosal and cutaneous haemorrhages, frank haematuria, life threatening haemolysis
17Life-threatening pulmonary haemorrhage requiring ventilation, mucosal bleeding
18Severe mucosal and cutaneous haemorrhages
19Severe sytemic infections, recent red cell transfusion requirement
ITP and AIN (+ acquired Glanzmann's)
20Widespread mucosal bleeding, severe systemic infections
21Extensive mucosal and cutaneous haemorrhages, red cell transfusion dependent

Treatment protocol Campath-1H is a genetically engineered, humanized monoclonal antibody (mAb) which has been derived by transplanting the hypervariable regions of the rat Campath-IgG monoclonal antibody into the human immunoglobulin genes (Reichmann et al, 1988). This monoclonal antibody recognizes and is specific for the CD52 antigen expressed on B and T lymphocytes, monocytes and eosinophils, but absent on other blood cells (Hale et al, 1990). Campath-1H was produced at the Therapeutic Antibody Centre, Oxford, UK.

All patients were admitted to St. George's Hospital for Campath-1H treatment. Pre-treatment assessment included a full blood count, biochemical screen, lymphocyte subsets, serum immunoglobulins, direct antiglobulin test, platelet- or granulocyte-specific antibodies for the appropriate cytopenia, a chest radiograph and electrocardiogram. A test dose of 1 mg of Campath-1H in 100 ml of normal saline was given intravenously over 1 h with full resuscitation equipment available. This was followed by a daily therapeutic dose of 10 mg/d for 10 d as an intravenous infusion given over 4 h in 250 ml of normal saline.

Reactions were treated with hydrocortisone and piriton, a reduction in the infusion rate and sometimes small doses of intravenous pethidine. In one patient, treatment was given subcutaneously following severe first day reactions. Treatment was not given in the presence of active bleeding (except in one patient), active infection, uncontrolled hypertension, heart failure or arrhythmias. All patients were treated with prophylactic oral ciprofloxacin, fluconazole, acyclovir and chlorhexidine mouthwashes. This continued for 4 to 6 weeks post treatment. All patients received only irradiated blood products from the start of Campath-1H and indefinitely thereafter. Campath-1H was followed routinely by cyclosporine (CSA) in seven patients, at a dose of between 2·5 and 5·0 mg/kg/d, with the aim of keeping whole blood trough levels around 75–150 μg/l. The CSA was commenced at the end of the course of Campath-1H, except in patient 6 in whom it was introduced at 5 months.

Granulocyte immunology A panel of Group O donors was selected which represented the following granulocyte-specific antigens; homozygous HNA-1a and HNA-1b and HNA-2a+, HNA-2a, HNA-3a+ and HNA-3a. These donors were also typed for HLA class I. Patient sera were incubated with granulocytes and lymphocytes in the following techniques: immunofluorescence tests (Decary et al, 1975; Verheugt et al, 1977), granulocyte chemiluminescence test (Lucas, 1994) and the monoclonal antibody immobilization of granulocyte antigen assay (Bux et al, 1993).

Platelet serology Patient sera were screened for platelet-reactive antibodies against a panel of four HPA- and HLA-typed platelets, recovered from frozen storage, using the indirect platelet immunofluorescence test (PIFT) (Von dem Borne et al, 1978). Determination of the glycoprotein specificity of platelet-reactive antibodies was carried out using the monoclonal antibody immobilization of platelet antigens (MAIPA) assay (Kiefel et al, 1987).

A definition of response for autoimmune neutropenia was a neutrophil count maintained > 0·5 × 109/l and a partial response defined as a neutrophil count of > 0·5 × 109/l with infrequent granulocyte colony-stimulating factor (G-CSF) (less than once weekly). Response to ITP was defined as a sustained platelet count of > 30 × 109/l over at least 3 months. For patients with autoimmune haemolytic anaemia, response was defined as red cell transfusion independence and discontinuation of prednisolone, and a partial response as either > 50% reduction in red cell transfusion requirements or requirement for small doses (< 10 mg/d) of prednisolone.


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

Response to Campath-1H

The response to treatment with Campath-1H is shown in Table III. Out of four patients with autoimmune neutropenia, a sustained response was seen in three, the fourth patient required continued but less frequent G-CSF. Of the four patients with autoimmune haemolytic anaemia, two had warm-type autoimmune haemolytic anaemia [direct antiglobulin test (DAGT) +ve IgG only] and both responded, although one had a mild relapse which required a modest increase in the dose of prednisolone to achieve a subsequent response. One patient with cold-type autoimmune haemolytic anaemia had a partial response with reduction in red cell transfusion requirements. The fourth patient, with autoimmune haemolytic anaemia (DAGT strongly positive for complement and weak IgG) and life-threatening intravascular haemolysis, showed no response to treatment with Campath-1H and subsequently died of intractable haemolysis and widespread systemic venous thrombosis. A response was seen in two out of four patients with red cell aplasia, although one patient relapsed in association with an acute renal allograft rejection episode when the CSA blood level was suboptimal. This patient is currently awaiting a second course of Campath-1H. A response was seen in two patients with Evan's syndrome but both relapsed, one responded to a second course of Campath-1H although relapsing again later. The third patient with Evan's syndrome had only a transient response. A patient with severe haemorrhages as a result of ITP and acquired Glanzmann's disease in association with autoimmune neutropenia had a sustained response apart from persistent, although asymptomatic, neutropenia. One patient with ITP and red cell aplasia had a response to ITP but relapsed 3 months later. A response was seen in two of the three patients with autoimmune pancytopenia, but both relapsed, one of whom responded to a second course of Campath-1H.

Table III.   Response to Campath-1H.
  Dead/Alive (D/A)Follow up (months)
  1. R, response; PR, partial response (see text for definition); NR, no response; Pred, prednisolone; VCR, vincristine; Aza, azathioprine; GCSF, granulocyte colony-stimulating factor.

1R at 2 weeksA61+
2PR, requires intermittent GCSFA31+
3R at 2 weeks, relapse of ITP at 9 months responded to Pred, Aza, VCRA29+
4R at 1 weekA21+
5R at 8 monthsA16+
6PR, partial relapse, R to small increase in Pred doseA11+
7PR, reduced transfusionsA5+
9R at 2 months, NHL transformed to high gradeD16
10R at 6 weeks, relapse at 7 months with acute renal rejection episodeA12+
13Died d +4 of Campath-1HD4 d
14R at 1 week, relapse at 3 months, R to CSA, relapse at 14 months, 2nd Campath-1H R at 1 week, relapse at 19 monthsA20+
15R d +3, relapse at 3 months, 2nd Campath-1H, R at 2 weeksD14
16Transient R onlyD80 d
17R at 9 month, relapse at 17 months, 2nd Campath-1H R at 22 months, relapse at 24 monthsD26
18R at 2 week, relapse at 2 monthsD4
20R of ITP and Glanzmann's, remains neutropenic but no symptomsA36+
21R of ITP at 1 month, relapse at 3 monthsA10+

A profound and predictable lymphopenia developed in all patients following Campath-1H treatment (see Table IV). CD20+ B-lymphocytes recovered by < 3–6 months. CD8+ T-lymphocytes recovered at variable times after treatment from 1–36 months. The median CD4+ T-lymphocyte count at last follow up after one course of Campath-1H was 0·14 × 109/l (range 0·015–0·56; normal range 0·71–1·31), but only one patient developed a mild viral infection with scattered vesicular lesions of the skin, which settled promptly with oral acyclovir. There was no correlation between the degree of CD4 lymphopenia and response or relapse.

Table IV.   Blood counts before and after Campath-1H (at last follow up).
 Pre-Campath-1HPost Campath-1H (at follow up)
  • *

    Count supported by transfusions.

  • Severe thrombocytopenia at diagnosis, platelet count normalized pre-Campath with IVIg, bleeding continued as a result of acquired Glanzmann's disease.

  • AIN, autoimmune neutropenia; AIHA, autoimmune haemolytic anaemia; PRCA, pure red cell aplasia; AIP, autoimmune pancytopenia; NK, not known or not done; plts, platelets; neut, neutrophils.

3122·9< 0·119514·84·814930·80·30·26

Tolerability and possible toxicities of Campath-1H

Campath-1H was well tolerated in all patients apart from first-day reactions, which occurred in most patients and comprised fever, rigors and chills. This first-day reaction was severe in only one patient. Patient 13 with ITP and B-cell non-Hodgkin's lymphoma (B-NHL) (in remission) had extensive and uncontrolled mucosal and cutaneous bleeding at the time of Campath-1H treatment, and developed a fatal intracranial haemorrhage on d +4.

Following Campath-1H treatment, the appearance of new autoantibodies was documented in two cases. One patient with autoimmune pancytopenia (patient 17) developed cerebral vein thrombosis at time of relapse at 17 months with a strongly positive IgG anticardiolipin antibody (ACLA) of 69 U/ml (normal range 0–12), positive ANA 1:160, low complement C4 and positive thyroid microsomal antibody with negative thyroid stimulating hormone (TSH) binding inhibitory antibody and normal thyroid function tests. This patient later developed Guillain–Barre syndrome. The second patient with AIN and a previous history of ITP relapsed at 9 months with ITP which was associated with ACLA 43 U/ml but no thrombosis, a weakly positive antinuclear antibody (ANA), normal C3 complement but low C4 at < 0·1 g/l and a positive DAGT without evidence of significant haemolysis. In both these patients, the DAGT also became positive for the first time after Campath-1H at 15 and 9 months respectively.

Tumour progression was noted in two patients after Campath-1H. One patient with Evan's syndrome (patient 15) who received two courses of Campath-1H, and who had had a lobar resection of small cell lung carcinoma 3 years previously, died of metastatic carcinoma 5 months after the second course of Campath-1H. This patient was a heavy smoker and continued to smoke throughout. A second patient (patient 9) with red cell aplasia in association with low-grade B-NHL, responded to Campath-1H but died from high-grade transformation of the NHL at 16 months.

Cause of death

Seven of the 21 patients died (see Table V). Two of the three patients with autoimmune pancytopenia died, one from complications of Guillain–Barre syndrome at 26 months, the other of TTP on d +71, probably associated with CSA therapy. Of the three patients with Evan's syndrome, two died; one with coexisting systemic lupus erythematosus (SLE) died from a cerebral haemorrhage, and the other from recurrence of lung cancer. The patient with ITP and uncontrolled haemorrhages at the time of Campath-1H treatment died as a result of a cerebral haemorrhage on d +4, and one patient with red cell aplasia in association with low-grade NHL died from high-grade transformation at 16 months while still in remission from the red cell aplasia. Lastly, one patient with autoimmune haemolytic anaemia died with severe intravascular haemolysis in association with severe systemic venous thrombosis. There was only one case in whom the cause of death (patient 13) was possibly associated with Campath-1H.

Table V.   Cause of death.
Patient number Diagnosis Cause of deathTime of death after Campath-1H treatment
  1. NHL, non-Hodgkin's lymphoma; TTP, thrombotic thrombocytopenic purpura.

13ITPCerebral haemorrhaged +4
17AIPGuillain–Barre syndrome26 months
18AIPTTPd +71
14Evan'sCerebral haemorrhaged +80
15Evan'sRecurrent bronchial carcinoma23 months
8AIHAIntractable intravascular haemolysis and systemic venous thrombosis4 months
9PRCANHL transformation16 months

Discontinuation of previous therapy

Following treatment with Campath-1H, it was possible to discontinue corticosteroids in 11 out of 14 surviving patients. All patients with autoimmune neutropenia had experienced severe side-effects with G-CSF, namely severe bone pain, chest pain, arrhythmias and, in one patient, sudden agranulocytosis occurring 2 weeks after the initial response to G-CSF. The neutrophil response seen in these patients following treatment with Campath-1H meant that further regular treatment with G-CSF could be avoided, except for one patient (patient 2) who required G-CSF once every 7–14 d with no further significant adverse reactions.


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

In this pilot study, we have shown that Campath-1H can induce clinical remission in some patients with severe, resistant and life-threatening autoimmune cytopenias who have failed to respond to conventional immunosuppression and/or splenectomy. The best responses were seen in patients with autoimmune neutropenia. A case report of patient 1 has previously been published (Killick et al, 1997). All other therapy for autoimmune neutropenia, such as prednisolone and G-CSF, could be withdrawn, apart from occasional G-CSF doses used by one patient despite always maintaining a neutrophil count > 0·5 × 109/l. Responses were also seen in some patients with red cell aplasia and autoimmune haemolytic anaemia. Although responses were seen in ITP that occurred in association with other cytopenias, relapses were frequent. Seven of the 21 patients died, reflecting the severity of the autoimmune cytopenias in this group of patients.

Campath-1H has been used extensively in the treatment of other autoimmune disorders such as rheumatoid arthritis (Isaacs et al, 1992), vasculitis (Mathieson et al, 1990; Lockwood et al, 1993) and Wegener's granulomatosis (Lockwood, 1998), in which it has been given as a short-term immunotherapy to replace long-term chemotherapy and/or allow tapering or withdrawal of corticosteroid therapy. It has also been used in bone marrow transplant recipients to prevent graft rejection and graft-versus-host disease (Hale & Waldman, 1994; Dickinson et al, 1997; Hale et al, 1998), and in the prevention and treatment of renal, liver and corneal graft rejection (Friend et al, 1989; Newman et al, 1995; Calne et al, 1998). The rationale behind the use of Campath-1H in this study was that T-lymphocytes are thought to play an important role in the pathogenesis of autoimmune cytopenias, as they are involved in the control of expansion of immunoglobulin-producing, auto-reactive B-lymphocyte clones. Along with improvement in the affected blood count, reduction or disappearance of the respective autoantibody was demonstrated after Campath-1H therapy. Campath-1H induced a profound lymphopenia. The B-lymphocytes recovered rapidly, the CD8+ T-lymphocytes more slowly, but a profound CD4+ lymphopenia persisted in all patients. In other reported studies in which Campath-1H has been used to treat patients with other autoimmune diseases, CD4+ T lymphopenia has persisted for several years (Brett et al, 1996).

Campath-1H, whether the first or second course, was well tolerated clinically apart from predictable first-day reactions. Despite the persistent and profound CD4+ T-lymphopenia, only one patient had a mild viral illness after treatment. Worsening thrombocytopenia has been previously reported in a patient with ITP treated with Campath-1G (Lim et al, 1993) and one patient with ITP in our study died on d +4 of Campath-1H treatment from intracranial haemorrhage, although this patient had severe generalized bleeding prior to Campath-1H. The use of Campath-1H in actively bleeding patients would therefore seem to be contraindicated. There were no cases of Epstein–Barr virus (EBV) lymphoproliferative disease, although this is less likely to occur than with patients who are treated with T lymphocyte-specific monoclonal antibodies. Similarly, there has been very low risk in bone marrow transplantation (BMT) recipients receiving Campath monoclonal antibodies (Hale & Waldmann, 1998). Two patients had tumour progression after treatment with Campath-1H. Although unproven, it is possible that these were the result of the immunosuppression caused by using Campath-1H. On relapse, additional autoantibodies were detected in two patients. This is a novel finding. The use of Campath-1H in the treatment of patients with multiple sclerosis has been associated with thyroid function abnormalities and antithyroid antibodies (Coles et al, 1995). It is possible that lymphocyte depletion caused by Campath-1H may remove cells which normally prevent autoimmunity, as seen in some experimental models (Saoudi et al, 1996). Alternatively, the appearance of new autoantibodies may be unrelated to the choice of treatment but rather to the nature of the disease.

In order to reduce the risk of relapse after Campath-1H treatment, most of our later patients received low-dose CSA after the course of Campath-1H. The rationale for this was based on the successful results reported in renal allograft recipients using peri-operative Campath-IH followed by low-dose CSA monotherapy to help prevent rejection and reduce the need for additional immunosuppressive drugs (Calne et al, 1998). Relapse of ITP after administration of the rat monoclonal antibody Campath-1G has been reported previously (Lim et al, 1993). The humanized monoclonal antibody, Campath-1H, has been shown in other studies to be less immunogenic, with the advantage that repeated courses may be given. Although we have not measured antiglobulin responses in our patients, re-treatment with Campath-1H was well tolerated and clinically effective.

Alternative therapeutic options to Campath-1H for the treatment of resistant autoimmune cytopenias include steroids, splenectomy, G-CSF for autoimmune neutropenia, cytotoxic immunosuppressants such as cyclophosphamide and azathioprine, and autologous peripheral blood stem cell transplantation. A high proportion of patients will respond to further courses of corticosteroids but many relapse on dose reduction. Long-term side-effects of corticosteroids, such as avascular necrosis and osteoporosis, may cause major morbidity. Splenectomy may be hazardous in severely thrombocytopenic patients and is associated with increased risk of overwhelming sepsis. Furthermore, response to splenectomy is often unpredictable in ITP and autoimmune haemolytic anaemia or patients may refuse to have a splenectomy (patients 6 and 15). G-CSF has been used successfully to treat autoimmune neutropenia but serious side-effects were observed in our patients, namely, chest pain, arrhythmias, sudden onset of agranulocytosis following initial response, and severe bone and muscle pains.

More recently, the use of high-dose immunosuppression with autologous peripheral blood stem cell (PBSC) rescue has been proposed for resistant autoimmune cytopenias as well as other autoimmune disorders. This may work by eliminating auto-reactive clones or by ‘resetting’ the immune system to induce tolerance towards self. While this approach may be effective, it is associated with a procedure-related mortality risk of 9% at 1 year (Potter et al, 1999; Tyndall et al, 1999). In view of the mortality observed in this series of patients, one could argue that autologous PBSC transplantation would have been an appropriate option, but there was only one case in whom death was possibly associated with Campath-1H itself. Furthermore, irradiation and high-dose cytotoxic immunosuppressive agents are associated with a risk of solid tumours and haematological malignancies later in life, in addition to infertility. Although the CD52 antigen is expressed on mature spermatozoa, it is not expressed on the developing gonadal tissue (Hale et al, 1993) and so infertility is not a predicted risk with Campath-1H antibody therapy.

We conclude that Campath-IH is an alternative and safe option in the treatment of patients with autoimmune cytopenias, allowing complete withdrawal of corticosteroid therapy in some cases. It may represent an effective alternative to cytotoxic immunosuppressive agents, stem cell transplantation and, possibly, splenectomy but further prospective studies are indicated to assess its efficacy more accurately in the different types of autoimmune cytopenias.


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References
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