TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA

1 . A method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19×CD3 bispecific single chain antibody construct to an adult patient in the need thereof.

2 . The method of claim 1 , wherein said acute lymphoblastic leukemia (ALL) is B-lineage acute lymphoblastic leukemia.

3 . The method of claim 1 , wherein said acute lymphoblastic leukemia (ALL) is refractory to chemotherapy in patients non-eligible for allogeneic hematopoietic stem cell transplantation.

4 . The method of claim 1 , followed by allogeneic hematopoietic stem cell transplantation or wherein said method replaces allogeneic hematopoietic stem cell transplantation in patients eligible for allogeneic hematopoietic stem cell transplantation.

5 . The method of claim 1 , wherein the method is for the treatment, amelioration or elimination of minimal residual disease (MRD) in a patient with acute lymphoblastic leukemia (ALL).

6 . The method of claim 5 , wherein said patient is MRD-positive in complete hematological remission.

7 . The method of claim 5 , wherein the administration of said pharmaceutical composition results in stable disease or converts MRD positive acute lymphoblastic leukemia (ALL) into an MRD negative status.

8 . The method of claim 5 , wherein MRD is measured with quantitative detection of individual rearrangements of immunoglobulin genes or T-cell receptor (TCR) rearrangements, or by bcr/abl fusion transcripts, or by t(4;11) translocations using PCR or FACS analysis.

9 . The method of claim 8 , wherein the ALL patient shows a bcr/abl or a t(4;11) translocation signal above detection limit and/or at least one marker by rearrangement with a sensitivity of>10 −4 .

10 . The method of claim 8 , wherein the time to molecular relapse detectable by the method is more than 4 months.

11 . The method of claim 1 , wherein the corresponding variable heavy chain regions (V H ) and the corresponding variable light chain regions (V L ) regions in said CD19×CD3 bispecific single chain antibody construct are arranged, from N-terminus to C-terminus, in the order, V L (CD19)-V H (CD19)-V H (CD3)-V L (CD3).

12 . The method of claim 11 , wherein said CD19×CD3 bispecific single chain antibody construct comprises an amino acid sequence as set forth in SEQ ID NO. 1.

13 . The method of claim 1 , wherein one treatment cycle is a 4-week continuous infusion.

14 . The method of claim 13 , wherein the treatment cycle is repeated at least three times, after determination of a MRD negative status (consolidation).

15 . The method of claim 1 , wherein the CD19×CD3 bispecific single chain antibody construct is to be administered in a daily dose of 5 μg to 100 μg per square meter patient body surface area.

16 . The method of claim 15 , wherein the CD19×CD3 bispecific single chain antibody construct is to be administered in a daily dose of 15 μg to 30 μg per square meter patient body surface area.

17 . (canceled)

18 . The method of claim 2 , wherein said B-lineage acute lymphoblastic leukemia is B-precursor acute lymphoblastic leukemia.

19 . The method of claim 11 , wherein said CD19×CD3 bispecific single chain antibody construct comprises an amino acid sequence at least 90% identical to SEQ ID NO. 1.

20 . The method of claim 11 , wherein said CD19×CD3 bispecific single chain antibody construct comprises an amino acid sequence at least 95% identical to SEQ ID NO. 1.

21 . The method of claim 13 , wherein the at least four weeks of continuous infusion is followed by at least a 2-week treatment-free interval.

22 . The method of claim 14 , wherein each treatment cycle is followed by at least a 2-week treatment-free interval.